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Scientists say: mitosis, this is when a cell divides into two identical cells.
One cell becomes two identical cells in the process called mitosis.
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By Bethany Brookshire
July 22, 2019 at 5:30 am
Mitosis (noun, “My-TOE-sis”)
This is a type of cell division where one cell splits into two identical cells. Mitosis is how our bodies grow and develop — our bodies grow larger by adding more cells. A cell prepares for mitosis by making an identical copy of its DNA — the instructions that the cell uses to perform all its tasks. Mitosis then takes place through a series of steps. These steps help guide the DNA to opposite ends of the cell. As the two copies of DNA move apart, the cell lengthens. Then, it pinches in the middle and divides into two. In the end, one DNA copy ends up in each new cell.
Mitosis is happening all around you. It’s probably happening inside you right now. Mitosis produces new cells in our bodies during growth. Cells in the gut also undergo mitosis, as stomach cells and intestine cells get replaced. Bones undergo mitosis to knit back together after they’ve been broken. When starfish regrow a lost arm, they do it through mitosis, building a new limb cell by cell. And some organisms — such as bacteria and hydras — reproduce by mitosis.
In a sentence
Student scientists sent cells to space, to compare mitosis in space with mitosis on Earth.
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There are an estimated 37.2 trillion cells in the average adult human body. 37.2 trillion is a staggering number, especially when we remember that we all develop from a single fertilized egg cell. So how does one cell become 37.2 trillion cells? Through mitosis.
Mitosis is the process of cell division, in which one cell produces two new daughter cells that are genetically identical to each other. Mitosis occurs during development, creating more cells that allow an organism to grow, but it also takes place throughout the lifetime of an organism, as means to replace old cells with new ones.
Defects during cell division can result in cells containing either too few or too many chromosomes, which are molecules of DNA. Human cells, for instance, have 23 pairs of chromosomes and either the loss or gain of a single chromosome can lead to developmental disorders and certain diseases like cancer. As such, the process of mitosis requires absolute accuracy.
Based on visual observations, mitosis is classically divided into five phases: prophase, prometaphase, metaphase, anaphase and telophase. Interphase is the cell cycle stage in between two cell divisions. This is the cell equivalent of half time during a game, and it allows the cell to grow and double its genetic content in preparation for mitosis.
Duplicated chromosomes are referred to as “sisters,” and they remain closely linked. The linkage is particularly strong at the center of the chromosome within a region known as the centromere, and this is why chromosomes often appear X-shaped. This X-shape becomes visible at the start of mitosis during Prophase, as the chromosomes condense, transitioning from a loose “spaghetti” form into “rods,” which helps prevent them from tangling up as the cell divides.
The primary goal of mitosis is then to line up the duplicated chromosomes in the middle of the cell (Metaphase), and to equally split them apart (Anaphase) so that both daughter cells receive the same number of chromosomes. A spider-like structure called the mitotic spindle supports this process. The spindle consists of microtubules that connect to the chromosomes and, by growing and shrinking, provide the forces required to separate the duplicated chromosomes from each other. While the chromosomes move to opposite poles, the center of the cell contracts during the last phase of mitosis (Telophase), pinching off the two new-born daughter cells.
Leah was even inspired to design mitosis shirts! You can find them in her shop here .
Contributed by Leah Bury, a postdoc at the Whitehead Institute in Cambridge, and our Featured Artist for June, 2018. To meet Leah and see more of her art, click here .
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What Is Mitosis?
The primary mechanism by which organisms generate new cells is through cell division. During this process, a single "parent" cell will divide and produce identical "daughter" cells. In this way, the parent cell passes on its genetic material to each of its daughter cells. First, however, the cells must duplicate their DNA. Mitosis is the process by which a cell segregates its duplicated DNA, ultimately dividing its nucleus into two.
Cell division is a universal process among living organisms. In 1855, Rudolf Virchow, a German researcher, made a fundamental observation about all living creatures: every cell originates from another cell, or " omnis cellula e cellula , " in the original Latin, as author Myron Shultz recounts in a 2008 article in the journal Emerging Infectious Diseases .
The mechanisms of cell division vary between prokaryotes and eukaryotes . Prokaryotes are single-celled organisms, such as bacteria and archaea. They have a simple internal structure with free-floating DNA. They use cell division as a method of asexual reproduction, in which the genetic makeup of the parent and resulting offspring are the same. One common mechanism of asexual reproduction in prokaryotes is binary fission. During this process, the parent cell duplicates its DNA and increases the volume of its cell contents. Eventually, a fissure emerges in the center of the cell, leading to the formation of two identical daughter cells.
The cells of eukaryotes, on the other hand, have an organized central compartment, called the nucleus, and other structures, such as mitochondria and chloroplasts. Most eukaryotic cells divide and produce identical copies of themselves by increasing their cell volume and duplicating their DNA through a series of defined phases known as the cell cycle. Since their DNA is contained within the nucleus, they undergo nuclear division as well. "Mitosis is defined as the division of a eukaryotic nucleus," said M. Andrew Hoyt , a professor of biology at Johns Hopkins University, "[though] many people use it to reflect the whole cell cycle that is used for cell duplication."
Like prokaryotes, single-celled eukaryotes, such as amoeba and yeast, also use cell division as a method of asexual reproduction. For complex multicellular eukaryotes like plants and animals, cell division is necessary for growth and the repair of damaged tissues. Eukaryotic cells can also undergo a specialized form of cell division called meiosis , which is necessary to produce reproductive cells like sperm cells, egg cells and spores.
Stages of the eukaryotic cell cycle
The eukaryotic cell cycle is a series of well-defined and carefully timed events that allow a cell to grow and divide. According to Geoffery Cooper, author of " The Cell: A Molecular Approach, 2nd Ed. " (Sinauer Associates, 2000) most eukaryotic cell cycles have four stages:
G1 phase (first gap phase): During this phase cells that are intended for mitosis, grow and carry out various metabolic activities.
S phase (synthesis phase): During this phase, the cell duplicates its DNA. Eukaryotic DNA is coiled around spherical histone proteins to create a rod-shaped structure called the chromosome . During the S phase, each chromosome generates its copy, or sister chromatid. The two sister chromatids fuse together at a point called the centromere, and the complex resembles the shape of the letter "X."
G2 phase (second gap phase): During this phase the cell continues to grow and generate proteins necessary for mitosis.
(G1, S and G2 phases are collectively referred to as "interphase.")
M phase (mitosis): Mitosis involves the segregation of the sister chromatids. A structure of protein filaments called the mitotic spindle hooks on to the centromere and begins to contract. This pulls the sister chromatids apart, slowly moving them to opposite poles of the cell. By the end of mitosis each pole of the cell has a complete set of chromosomes. The nuclear membrane reforms, and the cell divides in half, creating two identical daughter cells.
Chromosomes, become highly compacted during mitosis, and can be clearly seen as dense structures under the microscope.
The resulting daughter cells can re-enter G1 phase only if they are destined to divide. Not all cells need to divide continuously. For example, human nerve cells stop dividing in adults. The cells of internal organs like the liver and kidney divide only when needed: to replace dead or injured cells. Such types of cells enter the G0 phase (quiescent phase). They remain metabolically active and only move into the G1 phase of the cell cycle when they receive the necessary molecular signals, according to Cooper.
Stages of mitosis
Mitosis is divided into four stages , according to course materials from the University of Illinois at Chicago. The characteristic stages are also seen in the second half of meiosis.
Prophase: The duplicated chromosomes are compacted and can be easily visualized as sister chromatids. The mitotic spindle, a network of protein filaments, emerges from structures called centrioles, positioned at either end of the cell. The mitotic spindle is flexible and is made of microtubules, which are in turn made of the protein subunit, tubulin.
Metaphase: The nuclear membrane dissolves and the mitotic spindle latches on to the sister chromatids at the centromere. The mitotic spindle can now move the chromosomes around in the cell. "You can make an analogy to a girder that's holding up a skyscraper," said Hoyt. "Except the girder can assemble and disassemble very rapidly. They are structural elements that are extremely dynamic." By the end of metaphase, all the chromosomes are aligned in the middle of the cell.
Anaphase: The mitotic spindle contracts and pulls the sister chromatids apart. They begin to move to opposite ends of the cell.
Telophase: The chromosomes reach either end of the cell. The nuclear membrane forms again and the cell body splits into two (cytokinesis).
At the end of mitosis, one cell produces two genetically identical daughter cells.
Cell cycle regulation and cancer
The various events of the cell cycle are tightly regulated. If errors occur at any one stage, the cell can stop cell division from progressing. Such regulatory mechanisms are known as cell cycle checkpoints, according to Cooper. There are three checkpoints within the G1, G2 and M phases. Damaged DNA stops cell cycle progression in the G1 phase, ensuring that an aberrant cell will not be replicated. The G2 checkpoint responds to incorrectly duplicated, or damaged DNA. It prevents cells from moving into the M phase until the DNA is replicated correctly, or until the damage is repaired. The M phase checkpoint can halt the cell cycle in metaphase. It ensures that all the sister chromatids are properly hooked up to the mitotic spindle and that sister chromatids move towards opposite ends of the cell.
"If things go wrong and are not corrected, you end up with some cells that get extra chromosomes and some that are deficient," Hoyt said. "Often those cells have a genotype[DNA sequence] that won't support the life of the cell, and the will cell die. That's usually a good thing."
Sometimes, abnormal cells manage not only to survive, but also to proliferate. Most often, these cells are implicated in cancer. "It [the cell] may have an extra copy of a chromosome that has an oncogene on it. And that's going to start pushing the cell cycle forward when it shouldn't be going forward," Hoyt said. "That's a first step toward cancer progression." Cancerous cells are known to go through rampant and unregulated cell divisions.
The relationship between the cell cycle and cancer has led to the development of a class of cancer drugs that specifically target cancer cells during mitosis. According to anarticle published in 2012 in the journal Cell Death & Disease , "this strategy encompasses a prolonged arrest of cells in mitosis, culminating in mitotic cell death."
For example, microtubule poisons stop mitosis by targeting microtubules , the main component of the mitotic spindle. Damaging these thin, hollow, microscopic protein filaments ultimately prevents sister chromatids from being pulled apart. Examples of microtubule poisons are the medications paclitaxel (Taxol ) and vinca alkaloids , which are used to treat a range of cancers, including certain ovarian and breast cancers.
However, microtubule poisons are not without their limitations. According to a 2018 review article published in the journal EMBO Reports , these drugs can sometimes be toxic to brain cells, or cancer cells can become drug-resistant and avoid being killed. In an effort to find alternate solutions, researchers are looking to develop drugs that target other aspects of mitosis. In 2016, the Food and Drug Administration (FDA) approved the use of the new drug Palbociclib in combination with existing anti-cancer drugs to treat certain breast cancers. Palbociclib works by keeping cancer cells frozen in the G1 phase, according to a 2017 review article published in the journal Nature Reviews Cancer .
The compounds tested in clinical trials so far have had some success but have not been as effective as microtubule poisons, according to EMBO Reports. Nevertheless, targeting mitosis in the treatment of cancer remains an active area of research.
- The Biology Project (University of Arizona): The Cell Cycle & Mitosis Tutorial
- Biology4Kids.com: Mitosis — When Cells Split Apart
- Scitable (Nature): Mitosis
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Aparna Vidyasagar is a freelance science journalist who specializes in health and life sciences. Aparna has written for a number of publications, including New Scientist, Science, PBS SoCal, Mental Floss, and several others. Aparna has a doctorate in Cellular and Molecular Pathology from the University of Wisconsin-Madison, and also received a master’s degree and bachelor’s degree from the same university.
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Course: ap®︎/college biology > unit 4.
- Phases of the cell cycle
Phases of mitosis
What is mitosis.
- The chromosomes start to condense (making them easier to pull apart later on).
- The mitotic spindle begins to form. The spindle is a structure made of microtubules, strong fibers that are part of the cell’s “skeleton.” Its job is to organize the chromosomes and move them around during mitosis. The spindle grows between the centrosomes as they move apart.
- The nucleolus (or nucleoli, plural), a part of the nucleus where ribosomes are made, disappears. This is a sign that the nucleus is getting ready to break down.
- The chromosomes become even more condensed, so they are very compact.
- The nuclear envelope breaks down, releasing the chromosomes.
- The mitotic spindle grows more, and some of the microtubules start to “capture” chromosomes.
- All the chromosomes align at the metaphase plate (not a physical structure, just a term for the plane where the chromosomes line up).
- At this stage, the two kinetochores of each chromosome should be attached to microtubules from opposite spindle poles.
- The protein “glue” that holds the sister chromatids together is broken down, allowing them to separate. Each is now its own chromosome. The chromosomes of each pair are pulled towards opposite ends of the cell.
- Microtubules not attached to chromosomes elongate and push apart, separating the poles and making the cell longer.
- The mitotic spindle is broken down into its building blocks.
- Two new nuclei form, one for each set of chromosomes. Nuclear membranes and nucleoli reappear.
- The chromosomes begin to decondense and return to their “stringy” form.
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- Published: 07 January 2011
Mitosis – The story
Conly Rieder of the Wadsworth Center, Albany, NY, interviewed at the University of Exeter, UK, by James Wakefield and Herbert Macgregor, October 2010
- James Wakefield 1 ,
- Conly Rieder 2 &
- Herbert Macgregor 1
Chromosome Research volume 19 , pages 275–290 ( 2011 ) Cite this article
Working on a manuscript?
Conly Rieder has an established reputation not only as a world leader in research into the mechanisms of mitosis and cell division but also as an extraordinary modern microscopist. The sheer artistry and beauty of his portrayal of chromosomes and mitotic spindles as well as the amazing resolution and clarity of his electron micrographs sets a tough standard for any who aspire to follow in his footsteps. Coupled to these exceptional technical skills, Conly is a keenly logical and critical experimentalist and young people entering the field of cell science can learn a lot from the manner in which he has approached the unknowns of the mitotic cell cycle.
Conly spent the latter half of 2010 working in Bill Earnshaw’s laboratory in Edinburgh, Scotland. His visit coincided with our decision to prepare this Special Issue of Chromosome Research on Mitosis, so we took advantage of the opportunity to spend a couple of hours talking to him with a digital recorder on the table. What follows is a slightly edited version of that most enjoyable conversation.
Conly Rieder 2010
Were you always inclined to be a biologist?
Probably, but the passion took quite awhile to bloom. I was born in southern California and spent the majority of my first 22 years in and around the beach cities—mostly outdoors. When I was in high school I developed a real liking for biology which was my strongest subject. At that time I was mainly interested in forestry—because I loved hiking and fishing in the mountains and the environment.
When I graduated from high school in 1968 I had a choice—either be drafted into the army or go to college: no in between option. I enrolled in the University of California, Irvine, which was a brand new campus 7 miles from home. At the time it I had no clear idea of what to study so I opted for my strong suit. My dad was a retired Marine fighter pilot who was vehemently against the war in Vietnam, and he offered to cover my car insurance and tuition which was $57 a quarter if I paid for my room and board expenses. I worked full time while attending Irvine, first in a fast food restaurant and then in a medical library. Working and going to school full time was no fun but it taught me time discipline that came in very handy later. Three years into UCI’s Biological Sciences programme I still had no idea what I wanted to do so I decided to apply to medical schools like most of my friends—but I didn’t get into a single med school. Lucky for me I backed up my med school attempts with applications to graduate school, which I understood was free if you were accepted into a Ph.D. programme. I applied to several programmes, got into all of them, and chose the University of Oregon at Eugene. At the time I did not know what I wanted to work on, or even whether I would complete the programme. However, I felt that if I was going to get paid to go to school in a region which was known for its world-class skiing and fishing, I’d be a fool not to at least give it a shot. Although I was still keen on forestry and ecology, I was also very interested in electron microscopy (EM) and cell structure, visual topics on which I did some independent work in my last year at Irvine.
How did you develop an interest in microscopy and then later in mitosis?
In 1972 Andrew Bajer, who was born and educated in Poland, was conducting same-cell correlative light and EM studies on mitosis in Haemanthus endosperm at the University of Oregon. This laborious technique entailed using light microscopy (LM) to film a dividing cell and then rapidly fixing it at a desired stage for a subsequent serial section EM analysis. I wrote to Andrew the summer I graduated from UCI and said I was interested in structural biology and EM and that I had been accepted into the U of O and would be interested in working with him. I had excellent grades, a decent Graduate Record Exam score, and good letters of recommendation. I added that I could not come unless I received a fellowship. Andrew was friends with the highly regarded Drosophila geneticist, Ed Novitski, and between them and the Dean, Aaron Novick, they came up with a 4-year post as a teaching assistant. That fall I appeared at Andrews’s lab door and introduced myself. The first words out of his mouth as he stared at my chest (he was about a foot shorter than I was) were “I thought you were a woman”! Nevertheless he let me join his lab which at the time consisted of his wife (Jadwiga Mole-Bajer) and two female colleagues, one from France (Anne-Marie Lambert) and one from Spain (Consuelo de la Torre). My first big mistake as I started in his lab was to mention that I typed 80 words per minute—which immediately made me his editor and typist for the next 5 years. Fig. 2 Andrew Bajer at home Christmas 1995 Full size image Several months later I met with my advisory committee to define deficiencies in my background. They advised me to take a range of graduate courses during my first year, from ecology and histology to physical chemistry. They also assigned me my teaching duties, most of which were concerned with preparing and supervising laboratory practical classes. The first year was mostly taken up with teaching and classes, which included a lab-based course in EM. The next 3 years were a mix of teaching and research. Andrew had made his international reputation primarily on his award-winning time-lapse cinematographic movies of mitosis—some of which are still available. I found genetics, biochemistry and molecular-biology too detached and abstract, but I thought watching and documenting the various dynamic behaviours exhibited by cells was very cool. And the prospect of actually getting paid to learn LM and EM was very appealing. My goal at that time was simply to publish a paper, finish graduate school, and worry about the future later. My dad had a favourite saying which was “bloom where you are planted”, and I was now firmly planted in the biology department in Eugene, Oregon. Fortunately, James (Jim) Kezer worked right across the hall from Andrew Bajer. Fig. 3 Jim Kezer at his home ca. 1980 Full size image Jim was a very approachable zoologist with an expertise in amphibian cytogenetics. His passion was for opera, salamanders, newts and anything related to the nucleus, often in partnership with colleagues like Joe Gall and Herb Macgregor. I never met Joe or Herbert while at Oregon, but Kezer talked about them all the time. Jim’s infectious enthusiasm was definitely a major influence on my career. He taught me histology and nuclear cytology with a strong emphasis on lampbrush and polytene chromosomes. I was inspired by those classes and became good friends with Jim, and during the next 2 years I was also his teaching assistant for both classes. During the middle of my second year a fellow by the name of Takeshi Seto joined Jim’s lab on sabbatical from Japan. Takeshi was an amphibian cell culture expert and he taught me how to grow lung cells from the local newt ( Taricha granulosa ) which was abundant in the cool lakes and wet forests of Oregon. He thought they would be excellent material for studying mitosis because newts have some of the largest chromosomes in the animal kingdom and their lung cells are gigantic, grow very flat, and are optically clear. Although Andrew was a botanist who worked with plant endosperm, he thought it would be a good idea for me to work on mitosis in newts, which unlike Haemanthus are not seasonal. For the next 3 years I spent 70 h a week typing, culturing newt cells and filming 16-mm movies of mitosis. During this time I digested Andrew’s 1972 book on mitosis while babysitting my microscope and I also read as many other papers and books related to cell division as I could, starting with E.B. Wilson’s first edition (1896) classic “The Cell in Development and Heredity”. All this reading prompted me to write a library-based Master’s thesis in 1975 on how chromosomes move during mitosis. One motivation for getting my M.S. was that I got paid more money as a teaching assistant. There were positive and negative aspects of working in Andrews’s lab. It forced me to become an independent thinker and resourceful experimentalist. Other individuals were more influential on my graduate experience including Kezer and Robert Hard, the latter of whom joined Andrew’s lab as a post-doc during my third year. Andrew hated teaching. He viewed it as an unwelcome distraction from his research, and he used to start his classes at 8 a.m. sharp in Polish—few students lasted past the first week. To him, Ph.D. students were an obligation, not a passion, and he preferred working more with women than men. Throughout my 5 years in his lab he never took me to a scientific meeting because he said my hair was too long—and he insisted that I call him “Dr. Bajer” and not Andrew until I got my Ph.D. Besides asking me to type manuscripts, he left me mostly alone with instructions to approach his wife with any questions. Jadwiga (Visha) was an outstanding scientist in her own right and was the “hands” of the Bajer/Mole-Bajer team. She became a strong ally and graciously provided me with the supplies and tools required to do my work. It was a real learning experience working in Andrew’s lab, which was a staging ground for many very interesting events—some really, really funny and some not so funny. I’d love to write a book with Bob Hard on our time in Andrew’s lab and title it “The Mitotic Pole”. Fig. 4 The Northwestern rough skinned newt, Taricha granulosa , was abundant in the lakes and forests of Oregon. Cultures from its lung tissues produce extremely flat, large (250-μm diameter), optically clear cells that have many advantages for studying mitosis Full size image Andrew had many cryptic phrases of wisdom including the statement, uttered in response to my showing him new data, that “even a blind chicken can sometimes find a piece of corn if you put it in front of his nose”. His favourite saying, which I still don’t fully understand, was that “the cell is always speaking; the secret is to learn its language”. Frequently he generated what he thought were exciting ideas that Hard and I usually ended up wasting time on. One Monday when we showed up for work Andrew led us over to two huge plastic ice coolers each of which was about 4 ft long, 3 ft wide and 3 ft high. He was really excited as he lifted the lids off both to reveal two rare, giant white sturgeon heads, from 100+ year old 1,000 lb fish that he had caught in the Columbia River that weekend with a research permit. This was several years after Richard Weisenberg had shown that brains were the best source of tubulin for in-vitro microtubule re-assembly studies. At the time others were using cow or pig brains to isolate tubulin because they were readily available from local slaughter houses. Andrew thought it would be interesting to study tubulin that came from an ancient creature that had changed very little over their 175 million year history. His orders to us that morning were to remove the brains which we thought would contain a 20 year supply of tubulin. Many hours later, after much dissection and a rushed literature search, Hard and I discovered that despite their enormous size, the brains of these ancient fish consisted of half a dozen or so thumbnail size neuronal ganglia scattered throughout the volume of their cranium. We had to abort the project. The only salvageable aspect of the whole fiasco was that Andrew now had a lifetime supply of meat for his dogs. My graduate routine was to show up in the lab sometime before noon, try to avoid Andrew so I wouldn’t have to type anything, and film newt cells well into the night. I would record for about a month and then send the film off to be developed in a Hollywood studio. When it came back I would splice together the parts that I wanted to make a copy of—because you never ever worked from the original negative—and then send the negative off again so that a positive could be made for analysis. So it would be 3 months later before I could see what I had. By the time 3 years had gone by I had a pretty extensive library of films of mitosis. And of course I was looking at all kinds of behaviours, first in real-time and then in time-lapse, from nuclear envelope breakdown and chromosome mono-orientation, to chromosome congression, chromatid separation, anaphase, telophase, and cytokinesis. During this time I fell in love with mitosis. Fig. 5 This figure was constructed from individual frames of a time-lapse DIC video light microscopy series of mitosis in a newt lung cell, filmed on August 16, 1993. In the second frame, the nuclear envelope has just broken down to initiate prometaphase, the stage of spindle assembly. The cell is in metaphase with a fully formed spindle and congressed chromosomes in the upper right hand frame and has entered anaphase in the bottom left hand frame. It then undergoes telophase and cytokinesis in the last two frames. Newts are cold blooded and their cells grow best around room temperature. At 21°C, they take anywhere from 1 to 8 h to complete a division, depending on their degree of flatness. Time in minutes is relative to the first (00) frame. Scale bar in 00 = 10 μm Full size image
How did you decide where to go and who to work with during your post-doctoral years and how did that lead on to your first independent position?
By the time I graduated from Andrew’s lab he and I had established a mutual respect for one another and, in part to show his appreciation he lined me up with two post-doctoral offers from people I had never met. One was with R.D. (Bob) Allen at Dartmouth College who was pioneering high resolution differential interference contrast light microscopy (DIC LM), and who later was involved in the discovery of video-enhanced LM. The other was Hans Ris who was developing high voltage electron microscopy (HVEM) at the University of Wisconsin. Both had terrific reputations—Allen was one of the founders of the field of cell motility while Hans was a National Academy member who had used LM and stains to show that chloroplasts contained DNA and were likely endosymbionts. Both had published several papers on mitosis. I had had a pretty large dose of LM in Andrew’s lab so in May of 1977 my girlfriend (Susan Nowogrodzki and later my wife) and I moved to Madison to work on the structure of microtubule organising centres. I then spent 2 years defining the high resolution 3-D ultrastructure of various microtubule nucleating organelles, publishing 3 solo author and 3 collaborative papers none of which had Hans’s name on them. Hans was already a well-respected scientist and an extremely unselfish mentor, and he wanted me to be credited with my own work. At the beginning of my 3rd year my position with Hans expired and I moved to Gary Borisy’s lab so I could complete a time-consuming same-cell correlative HVEM study on kinetochore /HVEM study on kinetochore fibre formation in mammals. The result was that by the end of 1979, I had a number of first author papers and had established myself as one of only a handful of experts in the emerging field of biological HVEM. After 3 years in Madison I began to search for a position that would pay me more than $11,500 per year. My only other criterion was that it was as an independent researcher and not as an EM technician. I was fortunate in that several years earlier Donald Parsons of the Roswell Park Cancer Institute had convinced David Axelrod, who was then the New York State Commissioner of Health, to buy a 1.2 MeV HVEM which was to be housed in a new Public Health Laboratory within the newly constructed Empire State Plaza in downtown Albany. From 1975 to 1979 Parsons recruited a number of highly talented individuals to work on extracting the maximum information possible from the HVEM. These included Joachim Frank, Carmen Mannella, Tony Ratkowski, James Turner and Mike Marko— all of whom were mathematicians, physicists, or biophysicists. However, by late 1979 it was evident that NIH/NCRR, which supported the HVEMs run by Ris in Madison and Keith Porter in Boulder as National Biotechnological Resources, was not going to fund the Albany HVEM because it lacked a cell biologist. I was then recruited to fill this void. I have been in the same lab space 50 ft underground ever since and our HVEM is still functional 32 years later. Fig. 6 High-voltage electron micrograph, from a 0.25-μm thick section, through a centrosome found on the surface of a telophase nucleus in a PtK1 cell. This beautiful organelle consists of a mother and daughter centriole pair surrounded by a less electron dense “cloud” of pericentriolar material. During mitosis centrosomes nucleate radial (astral) arrays of microtubules involved in spindle assembly. Scale bar = 0.5 μm Full size image
Throughout your career you seem to have stayed ahead of advancing technology and used your skills to work on problems with a high tech approach. How have you been able to do this?
I’ve been working with big and expensive equipment since I was a post-doc, after which my affair with high technology continued primarily because I was in the right places at the right times. I was fortunate when I took my job at the Wadsworth Centre in Albany in that N.Y.S. funding allowed me to set up my lab with extremely specialised equipment and to hire extremely proficient technicians. Also, during that first year in Albany I spent several summer days at the Marine Biology Laboratory (MBL) in Woods Hole where I met Ted Salmon and Greenfield (Kip) Sluder—both of whom were ably trained in LM by Shinya Inoue. Fig. 7 Edward (Ted) Salmon and Greenfield (Kip) Sluder during a “block” party at the Rieder MBL Memorial Circle cabin on August 12, 2009 Full size image I realised, right away, that Woods Hole was a fulcrum of scientific activity and thought, and it was also the ideal place to escape the heat of Albany during the summer. It has great beaches, my wife and kids would love it, and I could schmooze as much as I wanted with scientists from all over the world. As a result the next year I persuaded the N.Y.S Commissioner of Health and the Director of the Wadsworth Centre to allow me to spend my summers at Woods Hole. This quickly led to collaborations with Kip on using the HVEM to answer questions about centriole replication in sea urchin and starfish zygotes. These were incredibly time consuming studies in which Kip used polarisation LM to follow individual fertilised sea urchin zygotes to a critical point, after which he fixed and embedded them. At this point I took over. To make such studies even feasible I had to develop some novel approaches which involved using LM to pre-screen the content of serial sections cut for HVEM. I’m sure I’m the only one that has ever serially sectioned one, let alone many, whole sea-urchin zygotes looking for centrioles—basically two needles in a haystack. Fig. 8 An indirect immunofluorescence image of a newt lung cell in prometaphase of mitosis after staining for microtubules ( yellow ), chromosomes ( blue ), and keratin ( red ). As the nuclear envelope broke down in this flat cell, several chromosomes ( bottom left hand corner ) came to lie away from the centrosomes and forming spindle. Live cell video-enhanced light microscopic studies on such “lost chromosomes” proved in the late 1980s that during spindle assembly microtubules that form the kinetochore fibers are derived from aster microtubules growing from the centrosomes. Scale bar =10 μm Full size image While in residence at the MBL in 1980 Inoué and R.D. Allen discovered video-enhanced LM which led directly to Ron Vale’s discovery several years later, also at the MBL, of the first non-axonemal microtubule motor protein (kinesin). The development of video LM changed the whole ball game for me—and with Ted’s help I established the necessary technology in my Wadsworth lab in the mid 1980’s. I then began to work in earnest on defining the behaviour of microtubules, centrosomes and kinetochores at high spatial and temporal resolution. My days of waiting months for my 16-mm films to be processed were over because I could now view events in time-lapse or real time immediately after recording them. In the spring of 1985 Ted and I travelled to UC Irvine to visit the NIH/NCRR Biotechnological Laser Microbeam Resource that had been established by Michael Berns, who pioneered the field of modern laser microsurgery. We were trying to determine the potential of the system for surgical studies on dividing newt cells. I think it was the first day when we discovered the “polar winds” which ejected chromosome fragments from the centrosome (spindle pole) regions. Mike’s system was configured so that the shutter and stage movements were controlled by a single joy-stick, and all operations took place in the dark with nanosecond pulses of green light obtained by frequency doubling the rather loud output of a neodymium:yttrium-aluminum-garnet laser. It was like playing shooting games in an arcade—complete with sound effects—and Ted and I had a lot of fun cutting chromosomes and following their subsequent behaviour. Over the next few years we returned periodically to Mike’s lab to conduct other studies. In early 1989 Lee Hartwell, who was working on his cell-cycle checkpoint concept, phoned to ask if there was any evidence that cells actually waited for all chromosomes to move to the spindle equator before initiating anaphase. I was working on kinetochore function and chromosome congression at the time, and was aware from my thesis days that Raymond Zirkle published an ASCB abstract on this very topic in 1970 (which he never worked up into a full paper). I told Lee that the answer was yes, but that the evidence was mostly anecdotal and the mechanism was completely unknown, and I gave him several references. After hanging up the phone I remember thinking—wow—I bet I could determine, using laser microsurgery, why anaphase only starts after all chromosomes congress. I put that idea aside and went on to finish what were at the time more-interesting ongoing studies. However, in 1993 I was able to convince the Director of the Wadsworth to purchase all of the many component parts needed to assemble my own DIC based laser microsurgery system, which we constructed in early 1994. As we were assembling the system I drew up a list of cool studies that we could conduct once it was up and running and the kinetochore checkpoint work (which we ultimately published as a series of papers in 1994/1995) was at the top of the list. I’ve been at the right place at the right time more than once. In May of 1990 I was invited along with Kip Sluder, Gary Borisy (currently the Director of the MBL), Lee Hartwell and about 15 other western scientists to attend a two-week conference in Leningrad, Russia organised in part by Bill Earnshaw who was then at Johns Hopkins. The conference took place during the “white nights”, when the sun never sets, and during this period I got no sleep and lost 20 lbs. There were many highlights, but one was touring the Hermitage with Alexey Khodjakov who at the time was a Ph.D. student in Moscow working on centrosomes. In 1993, after the failed coup attempt in Russia, Alexey wrote to Kip Sluder and me asking if we had any post-doc positions available. Lucky for me I did and Kip did not. Alexey joined my lab in 1994 in time to help clean up the kinetochore checkpoint work, and to initiate some of the other studies on my list. Then in late December of 1996 he came to me with the idea of using Green Fluorescent Protein (GFP), which had just been shown by Martin Chalfie to work as a fluorescence reporter in vivo , to selectively tag kinetochores and centrosomes. This was a terrific idea because by selectively lighting up an organelle it would eliminate a major ongoing problem which was the uncertainty in positioning sub-resolutional non-membrane bound structures during the ablation part of the microsurgery process. After re-configuring the laser system for fluorescence LM we published a proof of concept paper which we used as the basis for several experimental papers on centrosomes. Since then Alexey has continued independently to develop the approach to the point where he can now selectively remove a budding pro-centriole from the wall of its mother without damaging the original centriole. Fig. 9 Daughter centrioles can be ablated as they form in a replicating centrosome. a A HeLa (human epithelial) cell during S phase of the cell cycle. The centrosome ( arrows ), which is composed of two centrioles, is labeled via centrin/GFP expression. b A higher-magnification view of the centrosome reveals that both mother centrioles have already developed short daughters ( arrows ). Both daughter centrioles were irradiated ( cf . arrows in 00:00 and 00:01) with short series of laser pulses (~10 per centriole), and 43 min later, the cell was fixed for an EM analysis. c Serial-section EM revealed that both daughter centrioles were completely ablated while mother centrioles remained structurally intact. Time is in minutes: seconds. Reprinted from Methods in Cell Biology, Vol 82, Valentin Magidson, Jadranka Lončarek, Polla Hergert, Conly L. Rieder, Alexey Khodjakov, Laser microsurgery in the GFP-era—A cell biologist’s perspective, 239–266, 2007, with permission from Elsevier Full size image
So now it was the science motivating technology development
Actually, developing a particular technology to solve a specific set of problems has been at the core of my efforts since joining the Wadsworth. From 1980 to 2000 I was a key player in, and for 10 years the principal investigator of, a NIH/NCRR funded National Biotechnological Imaging Resource grant. The primary goal of NCRR funded Resources is to develop a particular technology or set of technologies in response to a proven driving need by the biomedical user community. As an example, although an HVEM can image all of the biology within a 1–2-μM thick section, it puts it all onto a single 2-D screen or negative—and it is impossible to extract 3-D information from single 2-D images. Early attempts at overcoming this problem, including stereo viewing of tilted images and specific staining, proved of limited value because they produced low resolution images applicable to a small set of problems. For most studies it remained impossible to extract the desired high resolution 3-D information contained within the section volume. To overcome this problem Joachim Frank, Bruce McEwen, Jim Turner, Mike Marko and I spent many years developing HVEM tomographic approaches for extracting useful high resolution 3D EM information from thick sections. One of the more notable papers that came from this effort was the first tomographic reconstruction of the mammalian kinetochore—an organelle that I had been working on since graduate school. Many scientists, including Mike and Bruce, still work on perfecting EM tomography which through the years has developed into a very powerful and useful technology. Since graduate school the focus of my work has been on motile phenomena of which mitosis is just one example. Early on I would seek collaborative projects on an aspect of motility that I could solve with the equipment and methodologies developed in my lab—but this was only after we brought the technology to the point with our own questions where it was of proven value. So during the first 20 years of my career I published papers on 10 or so different organisms—from various fungi, protists and strange flies that live in wasps, to sea urchins, starfish, newts, rat-kangaroo’s and humans. Of course one problem of relying on cutting edge technology is the incredible expense. Take the development and implementation of video-LM in the 1980’s for example. This awesome approach allowed us to shoot lengthy real-time or time lapse sequences and then play them back instantly, instead of having to send them off to the photolab and wait weeks for the result. Originally, the images were stored on VHS video tape which was quickly supplanted by optical memory disc recorders and then by computer hard drives. During a 3 year period in the late 1980’s we went through 3 optical memory disc recorders at around $35,000 each. We’d buy one and a year later a new, improved format would come out and we’d buy that one and the old one would suddenly become a door-stop (obsolete) because it was no longer supported. Later we had to buy various types of disc readers just to be able to maintain access to our data. It became evident early on that I needed a constant influx of around $200 K a year to maintain my equipment base, and that hasn’t changed.
Could the work that you have been doing recently been done in the 70s?
Work on mitosis during the 1970’s consisted primarily of LM descriptions of how chromosomes and other spindle components behaved in living cells, or what the various components look like at the EM level—even in yeast!. During that period, methods for identifying the molecules involved in mitosis were hit and miss and were limited to indirect immunofluorescence LM on dead cells. In the 1970’s biochemical studies on dividing cells were crude and focussed exclusively on lysed cell models which never faithfully recapitulated the process under study—and which told us more or less what we already knew from live cells. The breakthrough in this area did not come until the perfection of Xenopus oocyte extracts for spindle assembly in the mid to late 1980s. This, combined with information derived from the various genome projects, allowed one to determine whether a given protein was critical for spindle assembly by simply immunodepeleting it from the egg extract. When I was in graduate school I was absolutely convinced that the molecular basis for the “anaphase trigger”, the mechanism by which chromatids separate to initiate anaphase, would not be solved in my lifetime. This would have been true had I died in 1992, before Andrew Murray and others cracked the problem using Xenopus extracts and yeast genetics. The focus of my recent work is still on understanding the molecular basis for behaviours exhibited by dividing cells. Currently I’m working on how cells slip through mitosis when they cannot satisfy the mitotic checkpoint and why cancer, but not normal, cells die during mitosis in response to taxol. While the behaviours (slippage and death during mitosis) could have easily been defined with the time-lapse techniques available in the 1970’s, none of the current tools were available at the time to even start to understand their molecular basis.
What, in your opinion, does microscopy still have to offer in relation to progress in understanding cell division?
Well, the days of publishing meaningful non-molecular based LM or EM observations on a particular cell, process or behaviour are over. However, LM will continue to play a key role in defining the function of the many novel proteins cloned from the various genome projects, because it forms the basis for most primary screens for mutants or phenotypes associated with inhibiting, deleting or knocking down specific proteins. So microscopy is and will continue to be an important tool in defining which proteins are involved in mitosis, how their location changes during the process, and which of the many sub-processes that comprise mitosis these proteins are involved in. That being said, there is also an enormous amount of developmental work going on at the forefront of imaging with light. This includes hardware and software developments as well as specimen preparation procedures. Mitosis is comprised of a series of behaviours that need to be defined mechanistically at the molecular level. These behaviours can only be discovered and characterised by live cell imaging; and the more detailed the temporal and spatial characterization of a particular behaviour, the more accurate the resulting molecular model will be. We are now able to tag multiple proteins with different fluorophores without disrupting their function, so that they can be followed in 4-D with high temporal and spatial resolution for long periods without damaging the cell. It is a stunning Nobel-prize winning technology that has already forced a radical redefinition of how kinetochores behave. I predict that it will continue to evolve and will remain the most powerful approach for elucidating the mechanics of mitosis. State-of-the-art live cell imaging changes at warp speed and there is no doubt that the advances made in the future will keep young investigators busy on mitosis for generations to come. Most, if not all, of the more obvious behaviours exhibited by centrosomes, kinetochores and chromosomes during mitosis have been discovered. However, how the various proteins involved in mitosis interact and change position over time, and what this means, remain to be determined. These questions are approachable with Total Internal Reflection Fluorescence microscopy (TIRF), Fluorescence Resonant Energy Transfer microscopy (FRET) and other LM techniques under development. It’s worth noting that the molecular mechanism for correcting errors in kinetochore attachment, which I think is the most recent spectacular finding on mitosis, was discovered through a combination of yeast genetics and live cell 4-D imaging. I feel less enthusiastic about the future contribution of EM to mitosis research. I think it will be limited primarily to defining the high resolution structure of those molecules or macromolecular complexes involved in the process, that cannot be crystallised but that can be isolated in pure form. I say this because there are critical and difficult specimen preparation problems that need to be solved before EM can be used on sections of cells to more than simply confirm what is suspected from high resolution LM studies. The major problem is to know exactly where the proteins that you are interested in are in the EM image. Rapid developments in super resolution LM have largely supplanted the older EM immune-gold staining methods, which for the most part worked only with fixation protocols that destroyed high resolution structural relationships. Members of the Wadsworth and others are working on methods to mill frozen cells into slabs containing a specific area of interest, for 3-D vitreous tomography—a technique that could, in principle, provide a minimally distorted snapshot of where every molecule was at the time of freezing. However, for this to become useful, methods must be developed for identifying the molecules of interest within the images, i.e., generating contrast throughout the thickness of the specimen specifically for the protein(s) under investigation—since most proteins in non-fixed, non-stained vitreous thick samples are invisible in the EM. So, there is now an effort to figure out how to solve this issue but I’m not optimistic that it will be solved in the near future.
What do more unusual systems have to tell us about mitosis (and meiosis) that many of today’s investigators are missing, either because they simply don’t know about them or they can’t be bothered, or they are unfashionable? Are we too hooked on “model systems” that might seem more promising when looking for a cure for cancer and more appealing to funding agencies? I guess I’m thinking mainly about all those amazing things that were described by Wilson 100 years ago, many of them in insects.
The answer to this question depends on how you define mitosis and what you want to know about the process. Let’s focus for a minute on mitosis in humans and define it to include all of the events that occur during the cell cycle—because clearly what happens during mitosis is predicated on earlier events. In this case, our understanding of how human cells are driven into and out of mitosis is based primarily on discoveries in yeast, frogs and sea urchins. Much of what we know about how centrioles/centrosomes replicate in human cells came from studies in the worm and fly. Most of the kinases that drive spindle assembly and error correction in human cells, like auroa and polo, were discovered in flies. Finally, what we know about chromatid separation and exit from mitosis (telophase) in human cells has been garnered primarily from work on yeast and frog oocytes. I am unaware of any major discovery about mitosis in humans that has been made in human cells. Rather a handful of diverse model systems have contributed to how we currently understand the division process. Although some workers continue to use unusual “orphan” systems to study mitosis and meiosis, the number is dwindling. There are several reasons for this. First, for such systems to be generally useful their genomes must be sequenced. Second, they must also offer a clear advantage over existing proven systems like yeast, worms and flies that can be easily genetically manipulated. We now know that if you remove the centrosomes from fly or human cells they form functional bipolar spindles, and if you knock out the cytoplasmic dynein motor protein at the same time they form spindles that look like the ones formed by plants, leading to the inescapable conclusion that there are multiple “redundant” mechanisms for spindle assembly in animals: animal spindles really are just plant spindles with centrosomes and dynein. It is also clear that there are at least two mechanisms for generating the forces to move a chromosome: one is based in the kinetochore and the other along the kinetochore fibre or in the pole. Some cells (like crane fly spermatocytes and Xenopus oocytes) use primarily just one mechanism while vertebrate somatic cells use both to different degrees. When I was a student the dogma was that because an error free mitosis is so vital to all organisms, the underlying force producing mechanism (singular) that leads to chromosome segregation must therefore be highly conserved. As a result, conclusions from one system were automatically accepted as true for other systems, which in retrospect led to much confusion. Try as we did, for many years it was difficult to understand the meaning of Art Forer’s neat Ph.D. thesis observation that in crane fly spermatocytes, holes in kinetochore fibres created by a UV microbeam moved rapidly poleward. Similar holes created in vertebrate somatic cells did not appear to move. Little did we know at the time that in addition to a mechanism being “highly conserved”, fidelity can also be ensured by redundant mechanisms working to lesser or greater degrees at the same time. I view the morphological and behavioural variations in mitosis and meiosis, so carefully described by E.B. Wilson and later by Frans Schrader and his wife Sally-Hughes Schrader, to be largely manifestations of emphasising one mechanism for forming a spindle or moving a chromosome over another. The real issue is what do you choose as a reference point to compare these variations against? For those of us who require a healthy, constant renewable supply of funds for our labs, the reference must be the human system or one that has been shown by past work to be directly relevant to humans. That being said, there is a real tangible advantage in knowing the early literature and the behavioural diversity exhibited by different cells and organisms during mitosis/meiosis. A terrific example of this is Bruce Nicklas’s very cool 1995 Nature paper in which he showed that putting tension on the last kinetochore to attach to the spindle (by pulling on the chromosome) allows the mitotic checkpoint to be satisfied. The overlooked key to this study is that Bruce did it in mantid ( Tenodera aridifolia sinensis ) spermatocytes containing a non-natural univalent chromosome. Due to the error correction mechanism, these univalent chromosomes would never establish a stable connection to a spindle pole unless he stabilised the connection by pulling on the chromosome. Few know that Bruce worked with the Schrader’s at Columbia in the late 1950’s and was well aware not only that non-natural univalent chromosomes led to an arrest in meiosis, but also that they were prevalent in the mantid, an easily available organism in North Carolina. Now here is an individual who spent 45 years working on grasshopper spermatocytes, who because of his knowledge of the literature realised in 1994 that there was a natural solution to one of the major questions in the field at that time. The resulting paper was his only publication ever on the mantid! I seriously doubt that the reviewers asked him to confirm his findings in a more “acceptable” system before publication. The reason for this being that the key proteins for the mitotic checkpoint were discovered several years earlier in yeast and shown to be highly conserved. The fact that he answered the question in a meiotic system and not a mitotic one was irrelevant, because it is now generally accepted from experimental evidence that meiosis is simply two back to back mitoses, the first of which is modified by the bivalent character of the chromosomes. It’s interesting that Bruce’s paper contains no gels or biochemistry, but was based simply on live cell imaging, a microneedle and some indirect immunofluorescence studies! Fig. 10 Bruce Nicklas 2010 Full size image As exemplified by the Nicklas study, the diversity of spindle structure and chromosome behaviours exhibited during mitosis and meiosis can at times prove useful in problem solving. However their utility is predicated on first knowing the unique attributes of various organisms (like Bruce did) and these days few students read or study the older literature. Also, in my view, hypothesis-driven experimentation, which was mandatory for funding in the 1980’s to 1990’s, is being replaced by cook-book and largely automated isolations, purifications and rote characterizations of genes and their function. Since the unusual divisions you refer to are mostly interesting because they provide “natural” experiments, and since experimentation in biomedical research is no longer in vogue, there is little reason for students to study the diversity of mitoses except to satisfy their curiosity. Again, in my view, most students either don’t have the time or the inquisitive mind for this literary research. Theodosius Donzhanski once said “Nothing makes sense in biology except in the light of evolution”. Would it, in your view, be possible to construct the evolutionary story of mitosis—how it all began and how it evolved into the highly sophisticated process that we see in higher organisms today or have attempts already been made to do this and not proved especially rewarding?
This question is related to the previous one. Several attempts have been made to construct an evolutionary story of mitosis but there are too many missing links that doom such projects from the start. Evolution is clearly responsible for the redundant mechanisms seen in human cells for forming a spindle and moving chromosomes—any change that introduces a novel backup system that enhances the fidelity of mitosis will be selected for. However, the discovery of these redundant mechanisms did not come about through studying how the spindle evolved, but rather via experimentation on insect and vertebrate cells. Unfortunately, because it has little demonstrable impact on the public who pays the research bills, when and how these various mechanisms arose in evolutionary history have been relegated to interesting philosophical questions. As a result few in major research institutions work on the evolution of mitosis because their job, promotions and salary are directly linked to the amount of grant money they generate. Instead such issues are explored on shoe-string budgets, often in small liberal art colleges where such research forms a valuable part of the academic experience because of the skills it teaches. In my opinion rather than set out to construct the evolutionary story of mitosis from the literature or even new research, it would be better and much cheaper to simply wait for it to construct itself—because that’s slowly happening.
What were the most exciting moments of your career? Fig. 11 Cell fusion methods were used to create a rat kangaroo (PtK1) cell that contained two independent mitotic spindles. Live cell observations on such cells revealed that “wait anaphase” signal produced by unattached kinetochores is not diffusible and that its target is in or near the spindle containing the unattached kinetochores Full size image By far the most exciting times were those few short inspirational periods when I realised that the experiment I just thought up was not only doable but also a “win-win” situation, meaning that regardless of the outcome the result would be important and publishable in a top journal. As an example, after we found that unattached kinetochores released a “wait anaphase” signal I wondered whether this inhibitor was diffusible, or if it targeted something associated with the spindle. As I was pondering this question it dawned on me that the perfect way to discriminate between these possibilities would be to create a cell containing two independent spindles adjacent to each other, one of which possessed one or more unattached kinetochores at a time when the other had already satisfied the mitotic checkpoint. If the unattached kinetochores on one spindle inhibited anaphase in the neighbouring spindle that lacked an unattached kinetochore, then the inhibitor was diffusible. On the other hand, if the spindle lacking unattached kinetochores entered anaphase in the presence of a neighbour containing one or more unattached kinetochores, then the inhibitor was not diffusible and its target was near or in the spindle containing the unattached kinetochores. We used cell fusion to do the experiment and the result was clear—the wait anaphase signal generated by an unattached kinetochore is not diffusible and targets something associated with the spindle containing the unattached kinetochore. This experiment also showed that the “go anaphase” signal, generated after the mitotic checkpoint is satisfied, is diffusible and can force a spindle into anaphase even if it contains unattached kinetochores. Although this was a very satisfying experiment, it was too far ahead of its time as is evident from the fact that the 1997 paper reporting the result has been cited more in the past few years than in the years immediately after it came out.
There are now a bewildering number of molecules, all with their own special acronym that seem to be involved in regulating the various integrated processes involved in the mitotic cell cycle. Do you think the day will come when we will be able to put the jigsaw together and present a comprehensive description of the entire process, G1 through M, with a full understanding of the roles of each of the molecules involved?
In the headlong drive for reductionism and against the background of the enormous amount that is now known about mitosis, what questions remain? What’s left for the next generation of young-uns to get their teeth into and forge their reputations on? If I knew the answer to this question I wouldn’t retire!
Looking back on your life up to the time when you left Oregon, can you identify any transferrable skills, not in any way related to biology, that you were able to exploit in later years as an experimental biologist? When I was 12, I became a serious coin collector which involved spending hours looking at coin surfaces with a magnifying glass. This led to a keen appreciation and interest in minute details, which continues to this day. Later, due to family issues, I was forced to work full time while I attended undergraduate school. This taught me time-management skills that have proven extremely useful throughout my life. In a way this experience made me a bit impatient, so if a project we were working on did not show promise after 3 months, I simply bagged it and started a new one. I’m not much for banging my head against a wall—and that came from developing a real value for time when I was younger. Finally, during the last 2 years as an undergraduate I worked in a medical library, basically doing literature searches for MDs. This led to a keen appreciation for the history of a particular scientific problem, which as a graduate student led me to digest all I could on what was written about mitosis. I believe it fair to say that my colleagues still consider me to have an outstanding command of the early literature—at least up to about 1990 when it started to get out of hand.
What advice would you offer to those just entering the field? I tell most students to ask themselves “What do I want to be doing 5 years from now?”, and then work to make it happen because the time will go quickly! The consensus among my peers is that those who work 60-hr instead of 40-hr weeks as a graduate students and post-doc will ultimately get the better job—as long as they are using the time wisely. That being said the best advice I can give to someone interested in researching mitosis is to become wedded to the entire process and not to just a single molecule or avenue. That way you can rapidly change your plan of attack, without an inordinate amount of down time, if the avenue you are working on gets too crowded, suddenly comes to a dead end, or simply becomes boring. At appropriate times in your career you can also launch attacks along multiple avenues and then focus on those that look most promising. I also think it beneficial to find a cool cutting edge technology that you are interested in and learn it well. It may be that it is your experience with this technology, which every department wants and must have, that gets your foot in the door and not the actual biological problem you are working on. Finally, there is an increasing tendency to declare in a paper title a sexy conclusion that is supported entirely by indirect data—because such titles generate excitement and help with funding. However, they also start new avenues of research that all too frequently turn out to be dead ends, because the original conclusion(s) were erroneous from the start. Therefore be very critical when reading the literature and be especially critical of conclusions based entirely on indirect data like cell-sorting-based population studies and/or indirect immunofluorescence. Along these same lines, I’ve noticed an increasing tendency to not thoroughly do the appropriate homework before starting a project. Something is wrong with the claim that protein X is required for a functional mitotic checkpoint, when it is clear from earlier literature that knocking protein X out of mice has no phenotype while knocking bona-fide mitotic checkpoint proteins out is lethal at the embryonic stage.
Early 3-d hvem.
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High-Resolution LM work on Kinetochore Function
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Laser Based-Work on Chromosome Motion and Spindle Assembly
Rieder, C.L. , E.A. Davison, L.C.W. Jensen, L. Cassimeris, and E.D. Salmon. 1986. The oscillatory movements of mono-oriented chromosomes, and their position relative to the spindle pole, result from the ejection properties of the aster and half-spindle. J. Cell Biol ., 103 :581–591.
Khodjakov, A., R.W. Cole, B.R. Oakley and C.L. Rieder. 2000. Centrosome-independent mitotic spindle formation in vertebrates. Current Biol . 10 :59–67.
Kinetochore-Based Mitotic Checkpoint
Rieder, C.L ., R.W. Cole, A. Khodjakov and G. Sluder. 1995. The checkpoint delaying anaphase in response to chromosome mono-orientation is mediated by an inhibitory signal produced by unattached kinetochores. J. Cell Biol ., 130 941–948. A JCB Archive Paper
Rieder, C.L ., A. Khodjakov, L.V. Paliulis, T.M. Fortier, R.W. Cole and G. Sluder. 1997. Mitosis in vertebrate somatic cells with two spindles: Implications for the anaphase onset checkpoint and cleavage. Proc. Natl. Acad. Sci. USA . 94 :5107–5112.
Mitotic Checkpoint Slippage
Brito, D. and C.L. Rieder . 2006. Mitotic checkpoint slippage in vertebrates requires destruction of cyclin B but not of kinetochore-checkpoint proteins. Current Biology 16:1194–1200
Yang, Z., A.E. Kenny, D.A. Brito and C.L. Rieder . 2009. Cells satisfy the mitotic checkpoint in Taxol and do so faster in concentrations that stabilize syntelic attachments. J. Cell Biol ., 186:675–684.
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Conly Rieder of the New York State Department of Health, Wadsworth Center, Albany, NY, interviewed at the University of Exeter, UK, by James Wakefield and Herbert Macgregor, October 2010
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Wakefield, J., Rieder, C. & Macgregor, H. Mitosis – The story. Chromosome Res 19 , 275–290 (2011). https://doi.org/10.1007/s10577-010-9174-3
Published : 07 January 2011
Issue Date : April 2011
DOI : https://doi.org/10.1007/s10577-010-9174-3
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One of the many fibs our teachers told us for our own good is that animals are all the same at the cellular and molecular level despite their apparent outward differences. Thinking in that mindset, it's okay to study how ‘the cell' works without worrying too much about which particular cell one is considering. In addition to being helpful when preparing for exams in introductory biology courses, this fiction has practical benefits for scientists. Focusing on the features that cells have in common has enabled researchers to make great advances by studying the organisms most amenable to their question and method of choice, and to synthesize information to obtain coherent pictures of biological processes. In reality, there is variation throughout all of biology, including at the cellular and molecular levels, and even the most basic cellular processes, such as the mechanics of cell division, can differ dramatically between animal cells. There can even be large variations between different cells of the same organism: it has been known for more than a hundred years that spindles, the structures that segregate chromosomes during cell division, show great variations in size and shape over the course of development ( Wilson, 1897 ). Very little is understood about the origins of this variation—which might have important implications for development, evolution and human health. Now, writing in eLife , Jeremy Wilbur and Rebecca Heald of the University of California at Berkeley offer important insights into the mechanisms that underlie these changes in spindle morphology ( Wilbur and Heald, 2013 ).
Embryos undergo multiple rounds of rapid division during early development in many animals, and as the cells become progressively smaller, so too do the spindles that are responsible for their divisions ( Figure 1 ). Recent studies of these early divisions in Xenopus laevis ( Wuhr et al., 2008 ), C. elegans ( Hara and Kimura, 2009 ; Greenan et al., 2010 ) and mouse ( Courtois et al., 2012 ) have produced many interesting results, but the underlying causes of these changes in spindle size remain unclear. Since both cell size and spindle size decrease, it is tempting to think that there is some causative relationship between the two phenomena: that the confines of a smaller cell make spindles smaller, perhaps due to mechanics ( Hara and Kimura, 2009 ) or the depletion of a limiting pool of cytoplasmic components ( Goehring and Hyman, 2012 ). However, this is not the only possibility. It could be that changes in cellular biochemistry during early development give rise to smaller spindles through processes that are not connected to cell size. Understanding which of these scenarios is correct has been challenging.
Embryos undergo multiple rounds of rapid division during the early stages of development of many animals. As the cells become progressively smaller, the spindles inside them also decrease in size. Reproduced from Wilson (1897) .
FIGURE CREDIT: REPRODUCED FROM WILSON EB (1897).
To appreciate how fiendishly difficult this problem is, it is important to realize that the standard usage of two of the mainstays of modern cell biology research, namely inferring causation by 1) detecting co-occurrence of a protein and a phenotype and 2) perturbing the activity of a protein and examining the effect on a phenotype—cannot be used to rigorously establish the mechanisms controlling differences in spindle size. An extreme example illustrates this point: spindles are primarily composed of microtubules, which are in turn composed of the protein tubulin. Thus larger spindles contain more tubulin (co-occurrence) and depleting tubulin will reduce spindle size (perturbation), but this does not mean that changes in tubulin are responsible for changes in spindle size during development. Rather, these results suggest only that changes in tubulin could affect spindle size, not that they actually do so.
Wilbur and Heald overcome these difficulties through a powerful and conceptually straightforward approach: they prepare extracts from embryos at different developmental stages and assemble spindles in these extracts. They find that spindles in the extracts are the same size as the spindles in the embryos the extracts were made from, even though the extracts lack cell boundaries. This proves that changes in the size of the spindle are caused by changes in the state of the cytoplasm and are not directly controlled by cell size (at least in this system). This leads us naturally to the next question: how do changes in the cytoplasm produce changes in spindle size? To address this issue, Wilbur and Heald first characterize the behaviors of microtubules grown off of centrosomes—structures that nucleate microtubules—in the extracts. They observe that microtubule polymerization is similar in the different extracts, but that microtubules switch to a depolymerizing state, or ‘catastrophy’, at a higher rate in later stage extracts. It has been argued that modifying microtubule catastrophy rates can change spindle length ( Ohi et al., 2007 ; Loughlin et al., 2010 ), presumably by altering the lengths of microtubules, suggesting that the decrease in spindle length during early development might be caused by the increase in catastrophy rate. However, differences in microtubule lengths cannot be the whole story because spindles from early stage extracts are not just longer; they are also wider and appear denser, suggesting that they contain far more microtubules than late stage spindles.
Next, Wilbur and Heald use a candidate approach to attempt to discover which cytoplasmic factors are responsible for the differing rates of microtubule catastrophies in the different extracts. They identify one protein known to increase microtubule catastrophies, namely the kinesin-13, kif2a, as being enriched on spindles in late stage extracts, and use perturbation experiments to argue that kif2a contributes to the differences in spindle size. However, the concentration of kif2a is the same in early and late stage extracts, which means that if kif2a is causing differences in the extracts, this must be because its activity is being regulated differently. Wilbur and Heald provide evidence that this regulation could be performed by importin α, which inhibits kif2a. They argue that over successive cell divisions importin α becomes increasingly sequestered in membranes, causing the cytoplasmic concentration of free importin α to decrease. This leads to an increase in kif2a activity, and thus an increase in microtubule catastrophy rates. This is a clever suggestion, as it offers a possible mechanism by which cell biochemistry could indirectly readout changes in cell size, since smaller cells have a greater surface to volume ratio than larger cells. However, it is not clear why importin α would bind to membranes only after they have been deposited to form cell boundaries, and not earlier when they are in cytoplasmic stores.
Demonstrating that the changes in spindle size during early development are driven by the changing biochemistry of the cytoplasm is a landmark finding that pushes the field forward and allows new, more precise questions to be formulated. One issue that will be important to resolve is the extent to which these changes are multifactorial. Are the differences in spindle structure primarily caused by one or two keys factors, or are large numbers of factors involved, each contributing a little, perhaps in opposing directions? Wilbur and Heald's study provides a hint that the situation may be complicated: they found that spindles from early stage extracts are enriched for the kinesin-13, MCAK. This suggests that MCAK may be more active in early developmental stages—a change that goes the ‘wrong’ way, as MCAK is known to increase catastrophy rates, whereas microtubules in the early stage extracts have a decreased rate of catastrophies . In any case, more work remains in the young and challenging area of studying how cell biology differs in different cells.
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Mitotic spindle scaling during xenopus development by kif2a and importin α, further reading.
- Developmental Biology
Early development of many animals is characterized by rapid cleavages that dramatically decrease cell size, but how the mitotic spindle adapts to changing cell dimensions is not understood. To identify mechanisms that scale the spindle during Xenopus laevis embryogenesis, we established an in vitro system using cytoplasmic extracts prepared from embryos that recapitulates in vivo spindle size differences between stage 3 (4 cells, 37 µm) and stage 8 (∼4000 cells, 18 µm). We identified the kinesin-13 kif2a as a driver of developmental spindle scaling whose microtubule-destabilizing activity is inhibited in stage 3 spindles by the transport receptor importin α, and activated in stage 8 when importin α partitions to a membrane pool. Altering spindle size in developing embryos impaired spindle orientation during metaphase, but chromosome segregation remained robust. Thus, spindle size in Xenopus development is coupled to cell size through a ratiometric mechanism controlling microtubule destabilization.
Glucagon-like peptide-1 receptor activation stimulates PKA-mediated phosphorylation of Raptor and this contributes to the weight loss effect of liraglutide
The canonical target of the glucagon-like peptide-1 receptor (GLP-1R), Protein Kinase A (PKA), has been shown to stimulate mechanistic Target of Rapamycin Complex 1 (mTORC1) by phosphorylating the mTOR-regulating protein Raptor at Ser 791 following β-adrenergic stimulation. The objective of these studies is to test whether GLP-1R agonists similarly stimulate mTORC1 via PKA phosphorylation of Raptor at Ser 791 and whether this contributes to the weight loss effect of the therapeutic GLP-1R agonist liraglutide. We measured phosphorylation of the mTORC1 signaling target ribosomal protein S6 in Chinese Hamster Ovary cells expressing GLP-1R (CHO-Glp1r) treated with liraglutide in combination with PKA inhibitors. We also assessed liraglutide-mediated phosphorylation of the PKA substrate RRXS*/T* motif in CHO-Glp1r cells expressing Myc-tagged wild-type (WT) Raptor or a PKA-resistant (Ser 791 Ala) Raptor mutant. Finally, we measured the body weight response to liraglutide in WT mice and mice with a targeted knock-in of PKA-resistant Ser 791 Ala Raptor. Liraglutide increased phosphorylation of S6 and the PKA motif in WT Raptor in a PKA-dependent manner but failed to stimulate phosphorylation of the PKA motif in Ser 791 Ala Raptor in CHO-Glp1r cells. Lean Ser 791 Ala Raptor knock-in mice were resistant to liraglutide-induced weight loss but not setmelanotide-induced (melanocortin-4 receptor-dependent) weight loss. Diet-induced obese Ser 791 Ala Raptor knock-in mice were not resistant to liraglutide-induced weight loss; however, there was weight-dependent variation such that there was a tendency for obese Ser 791 Ala Raptor knock-in mice of lower relative body weight to be resistant to liraglutide-induced weight loss compared to weight-matched controls. Together, these findings suggest that PKA-mediated phosphorylation of Raptor at Ser 791 contributes to liraglutide-induced weight loss.
Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human
Cylicins are testis-specific proteins, which are exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 ( Cylc1/CYLC1 ) and the autosomal Cylicin 2 ( Cylc2/CYLC2 ) genes, have been identified. Cylicins are cytoskeletal proteins with an overall positive charge due to lysine-rich repeats. While Cylicins have been localized in the acrosomal region of round spermatids, they resemble a major component of the calyx within the perinuclear theca at the posterior part of mature sperm nuclei. However, the role of Cylicins during spermiogenesis has not yet been investigated. Here, we applied CRISPR/Cas9-mediated gene editing in zygotes to establish Cylc1- and Cylc2 -deficient mouse lines as a model to study the function of these proteins. Cylc1 deficiency resulted in male subfertility, whereas Cylc2 -/- , Cylc1 -/y Cylc2 +/- , and Cylc1 -/y Cylc2 -/- males were infertile. Phenotypical characterization revealed that loss of Cylicins prevents proper calyx assembly during spermiogenesis. This results in decreased epididymal sperm counts, impaired shedding of excess cytoplasm, and severe structural malformations, ultimately resulting in impaired sperm motility. Furthermore, exome sequencing identified an infertile man with a hemizygous variant in CYLC1 and a heterozygous variant in CYLC2 , displaying morphological abnormalities of the sperm including the absence of the acrosome. Thus, our study highlights the relevance and importance of Cylicins for spermiogenic remodeling and male fertility in human and mouse, and provides the basis for further studies on unraveling the complex molecular interactions between perinuclear theca proteins required during spermiogenesis.
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- J Oral Maxillofac Pathol
- v.18(Suppl 1); 2014 Sep
MITOSIS AT A GLANCE
Radhika m bavle.
Editor-in-Chief-JOMFP, Department of Oral and Maxillofacial Pathology, Krishnadevaraya College of Dental Sciences, Bangalore - 562 157, Karnataka, India. E-mail: [email protected]
NEOPLASM is an abnormal and un-coordinated growth of tissue, which is categorized by WHO (World Health Organization) as benign tumors, in-situ tumors, malignant tumors, and neoplasms of uncertain or unknown behavior.[ 1 ]
Cancer is a malignant tumor featuring abnormal cell growth and cellular division resulting in excessive cellular proliferation, with the potential to invade or spread to other parts of the body.[ 2 , 3 ] Dysplasia is linked to altered tissue architecture, with one of the reasons being excessive cellular proliferation, leading in all probability to malignant transformation if not treated.[ 4 ]
The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication (replication) that produces two daughter cells.[ 5 ]
Cell division occurs in defined stages, which together comprise the cell cycle [ Figure 1 ]. There are two types of cell division: Meiosis and Mitosis.
Cell cycle illustration with duration, regulation, and inhibitors
- MEIOSIS: Occurs during formation of the gametes, the number of chromosomes reduced to half in reproductive cell[ 6 ]
- MITOSIS: Mitosis is the process in which a eukaryotic cell nucleus splits in two, followed by division of the parent cell into two daughter cells.[ 6 ]
CELL CYCLE: Divided into two major events,[ 5 ]
- Interphase- Cell increases in size and replicates its genetic material
- G 0 phase- A resting phase where the cell has stopped dividing[ 5 ]
- G 1 phase- Cells increase in size in Gap 1. The G1 checkpoint control mechanism ensures that everything is ready for DNA synthesis[ 5 ]
- S phase- DNA replication occurs during this phase[ 5 ]
- G 2 phase- During the gap between DNA synthesis and mitosis, the cell will continue to grow. The G2 checkpoint control mechanism ensures that everything is ready to enter the M (mitosis) phase and divide[ 5 ]
- MITOSIS is subdivided into
(a) Photomicrograph (H&E stain, ×400) (b) hand drawn illustration showing prophase of mitosis with condensed nuclear chromatin
(a) Photomicrograph (H&E stain, ×400) (b) hand drawn illustration showing metaphase in mitosis
(a) Photomicrograph (H&E stain, ×400) (b) hand drawn illustration showing division of chromosomal material in anaphase of mitosis
(a) Photomicrograph (H&E stain, ×400) (b) hand drawn illustration showing telophase in mitosis with complete division and formation of a new set of daughter cells
NORMAL MITOSIS:[ 7 ]
Mitosis occurs in the following circumstances:
- Development and growth
- Cell replacement, repair, and regeneration
- Asexual reproduction in some micro-organisms.
The turnover rate of oral mucosa ranges from 14 - 24 days depending on the site (buccal mucosa, floor of the mouth, etc.). Oral mucosa is a highly dynamic tissue that rapidly replaces its structure and contributes to oral health by maintaining an intact barrier that protects the underlying tissues from environmental stress. Mucosal renewal and repair depends on stem cells or basal or mother cells. Only stem cells have the ability to continuously generate new cells for whole lifetime and when they divide they both renew themselves and produce hierarchies of other cells that differentiate for tissue function.[ 8 ]
Defects of mitosis result in various nuclear abnormalities, namely, micronuclei, binucleation, broken egg appearance, pyknotic nuclei, and increased numbers of and/or abnormal mitotic figures.[ 9 ]
These abnormal mitotic figures (MFs) are commonly seen in oral epithelial dysplasia and squamous cell carcinoma. Location and increased numbers of and/or abnormal mitotic figures are important criteria that carry increased weightage in the grading of dysplasias.[ 9 ]
Mitotic activity remains restricted to somatic stem cells that eventually repair injuries, and to committed stem cells that substitute for tissue turnover.[ 4 ]
The following are the criteria that characterize aberrations from regular mitotic activity in the soma:[ 4 ]
- Dislocated divisions with relentless persistency
(a) Photomicrograph (H&E stain, ×400) (b) hand drawn illustration showing abnormal mitosis with tripod formation
(a) Photomicrograph(H&E stain, ×400) (b) hand drawn illustration showing abnormal mitosis with tetrapod formation
- Centromere defects and chromosome misaggregation resulting in multiple mitotic figures
- Spindle defects- Aberrant cellular divisions
- Genome instability (Failures in check points and apoptotic system) resulting in proliferation and aberrant chromosome division figures (CDFs)
- Chromosome mutations- Acquisition of successive mutations leading to tumor initiation or syndromic manifestations
- Interphase aneuploidy
- Chromosome division figures- Pathologic mitosis with aberrant DNA content.
The hypothesis on the understanding of mitosis is as an equational bipartition of the hereditary substance (Fleming 1879; Roux 1883). True mitoses guarantee the constancy of terminally differentiated tissues.[ 4 ]
Cellular division can be:
Stem cells are capable of two types of symmetric divisions: A proliferation division resulting in the creation of two stem cells, and a differentiation division resulting in the creation of two differentiated cells[ 10 ] [ Figure 8 ].
Types of cell division - asymmetric and symmetric cell division
Asymmetric cell division [ Figure 8 ] is suspected to play an important role in cancer, in particular with respect to the cancer stem cell hypothesis. The hypothesis states in essence that each tumor contains a relatively small population of cells capable of initiating and maintaining tumor growth. This hypothesis has enormous therapeutic implications, but also raises the possibility that defects in stem cell lineages may lead to tumor formation. Cancer stem cells as well as normal embryonic and adult stem cells are defined by both their ability to make more stem cells, a property known as self-renewal, and their ability to produce cells that differentiate. One strategy by which cancer stem cells can accomplish these two tasks is asymmetric cell division. Asymmetric division is a key mechanism to ensure tissue homeostasis.[ 10 ]
In normal stem and progenitor cells, asymmetric cell division balances proliferation and self-renewal with cell-cycle exit and differentiation. Disruption of asymmetric cell division leads to aberrant self-renewal and impairs differentiation, and could therefore constitute an early step in the tumorigenic transformation of stem and progenitor cells and result in formation of atypical/multipolar mitosis (According to studies done by Arnold (1879), von Hansemann (1890), Mendelsohn). The pathology of premalignant and malignant tumors is the given homeland for the pathology of mitosis.[ 11 ]
Stroebe (1892) described asymmetric mitosis occurrence in carcinoma and sarcoma and in normal regenerating and inflammatory tissues.[ 11 ]
Stains to visualize CDFs and atypical and typical mitotic figures include H and E, Crystal violet, toluidine blue, Giemsa stain and fluorescent microscopy. Newer prognosticators like immunohistochemistry, flow cytometry, autoradiography, and DNA ploidy measurements are now on the forefront.[ 9 ]
The immunohistochemical labeling of MFs with the mitosis-specific antibody anti–phosphohistone H3 (PHH3) has been suggested as a promising method.[ 12 ]
Anti-PHH3 antibodies specifically detect the core protein histone H3 only when phosphorylated at serine 10 (Ser10) or serine 28 (Ser28). The phosphorylation of histone H3 is a rare event in interphase cells but a process almost exclusively occurring during mitosis.[ 12 ]
- Staff, Department of Oral and Maxillofacial Pathology, Krishnadevaraya College of Dental Sciences, Bangalore
- Dr. Shruti Singh and Dr. Padmalatha G.V, Postgraduate students, Department of Oral and Maxillofacial Pathology, Krishnadevaraya College of Dental Sciences, Bangalore.
Source of Support: Nil.
Conflict of Interest: None declared.
Meiosis vs. Mitosis: Unraveling Cell Division
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In the beginning, you were just some genetic material . In order to make you, your biological mom and dad both had to participate in an effort to pitch in one gamete each — a sperm cell and an egg cell, each with 23 chromosomes .
Here's where some complicated genetic juju had to go down — a process called mitosis, as well as its sister process, meiosis, which is equally important, but not as common. So wait ... meiosis versus meitosis ? What's the difference?
What Is Mitosis?
What is meiosis, what's the difference between meiosis and mitosis, visualizing chromosome separation, the purpose of meiosis.
Mitosis is a fundamental process in cell biology, driving the division of a single cell into two daughter cells. Cell division ensures that an organism's body cells continue to thrive and replace damaged or worn-out cells.
Thanks to mitosis, we're able to generate identical copies of cells, such as those used in tissue repair and growth.
The Process of Mitosis
During mitosis, a diploid parent cell undergoes a series of events. The nucleus of the parent cell divides, culminating in the formation of two genetically identical diploid somatic cells, or daughter cells.
This means that each daughter cell possesses an exact copy of the parent cell's genetic material, with the same chromosome number and genetic information.
One of the key players in this process includes the mitotic spindle, a complex structure of spindle microtubules that guides the orderly separation of chromosomes.
As the chromosomes line up along the metaphase plate, they undergo precise segregation into the two daughter cells during anaphase. Meanwhile, the nuclear membrane disassembles and reassembles, ensuring a smooth transition.
The Importance of Mitosis
Mitosis is essential for the growth, repair, and maintenance of multicellular organisms. It allows for the constant renewal of cells like skin, blood, and muscle, all while ensuring that these new cells are genetically identical to their parent cells.
In essence, mitosis is the cellular workhorse that keeps our bodies functioning smoothly.
Meiosis is a pivotal process in sexual reproduction, distinct from mitosis, as it aims to create genetic diversity.
Meiosis begins with a diploid parent cell, but it doesn't stop at just two daughter cells. Instead, it proceeds through two distinct stages: Meiosis I and Meiosis II.
Meiosis I: Exchanging Genetic Material
The initial stage, Meiosis I, involves a crucial step: homologous recombination, where homologous chromosomes from each parent exchange genetic material. This process shuffles the genetic deck, mixing and matching alleles (versions of genes) from both parents.
As a result of Meiosis I, two haploid daughter cells emerge, each with a unique combination of genetic material. These cells only possess one version of each gene, as opposed to the two versions found in a diploid cell. But the genetic diversity doesn't end there.
Meiosis II: The Formation of Gametes
Meiosis II follows, and haploid cells divide further. This second division results in four haploid daughter cells, each with distinct genetic compositions. These specialized cells are known as gametes, or sex cells, and they play a pivotal role in sexual reproduction.
During fertilization, reproductive cells (i.e., sperm cells) carrying their own unique genetic information fuse with egg cells, similarly loaded with distinctive genetic material. This union results in a zygotes with a complete set of genes, comprising contributions from both parents.
Meiosis is the architect of genetic variation, enhancing an organism's adaptability to a changing world. The meiotic process ensures that every sexual reproduction event yields genetic combinations that are truly unique — a crucial element in the creation of each new generation.
"The key to understanding the difference between mitosis and meiosis is not in the steps, but in the final products of each," says Brandon Jackson, assistant professor in the Department of Biological and Environmental Sciences at Virginia's Longwood University.
"Mitosis results in two identical 'daughter' cells, each with two versions of every gene — one version from each parent, just like every cell in the body," he continues. "Meiosis results in four cells called gametes — sex cells — but each has only one version of each gene. This way, when sperm and egg fuse during fertilization, the resulting zygote is back to having two versions of each gene."
So, if cells are dividing, it's almost always through mitosis, unless the product is a gamete that's planning to meet up with another gamete to make a new organism.
In this case, each cell can only have 23 chromosomes instead of the normal 46. So, some shuffling needs to happen in order to make sure each sex cell has half the chromosomes of a normal cell.
It's difficult to describe the differences between the processes of mitosis and meiosis without using terms like 'homologous recombination' and "cytokinesis," which are confusing. It helps to stop thinking about cell division in terms of chromosomes for a moment and, start thinking about sentences.
"Mitosis versus meiosis is my students' nemesis!" says Jackson. "But since DNA is a lot like words strung together to make sentences, we can use words to analogize these events."
One exercise Jackson does in his biology classes involves taking two sentences and calling them "chromosomes." For the sake of this article, we made Sentence 1 bold to make it easy to follow its path through the processes of mitosis and meiosis.
Both these sentences describe basically the same idea, but Sentence 1 (an egg cell, with 23 chromosomes) comes from the female parent (in bold), and Sentence 2 (a sperm cell, also with 23 chromosomes) comes from the male parent.
Both mitosis and meiosis start from here and duplicate the DNA, giving us two of each sentence.
The next step of mitosis separates the duplicates, and then sorts them back out to create twin cells that each contain genetic material inherited from both mother and father. Those can later make duplicates of themselves that are pretty much exactly like the duplicates your red blood cells or liver cells made last year or 20 years ago.
The first stage of meiosis , (scientifically known as Meiosis I), takes the duplicated DNA that marks the beginning of the mitosis process, copies it, which results in two daughter cells, each containing with full sets of chromosomes and then shuffles them up like a deck of cards:
The first step (scientifically known as Meiosis I) is when a single cell is copied resulting in two daughter cells, each containing a full set of chromosomes.
The second step (scientifically known as Meiosis II) then separates the new daughter cells, putting each into its own cell, leaving four cells with different DNA in each.
"Each sentence says the same thing, but with different versions of each word — each version being an allele, in DNA speak," says Jackson. "Each allele is a mix of words from the male and female parents."
Phew! Meiosis seems like a whole lot of work! Why go through the hassle when you could just do some quick mitosis and be done with it?
"Variation!" says Jackson. "This is the first part of sexual reproduction, the point of which is to increase genetic variation, and this increases an organism's ability to continue to adapt to a changing world."
Let's say the last gamete above (those are the "sentences" formed by meiosis) fertilizes another gamete that says,
That would make a new cell and organism with the following DNA profile:
Not only is that different than our parent cell, the one we started with, but it's different than either of the grandparents.
And if you have dozens of these sentences — humans have 23 pairs of "sentences," after all — and each sentence has thousands of words, every meiosis and fertilization event results in genetic combinations that have probably never existed.
Which is, of course, why you're so special.
Meiosis was first observed in sea urchin eggs in 1876 by the German biologist Oscar Hertwig.
This article was updated in conjunction with AI technology, then fact-checked and edited by a HowStuffWorks editor.
Frequently Asked Questions
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Sat / act prep online guides and tips, the 4 mitosis phases: prophase, metaphase, anaphase, telophase.
In order to heal an injury, your body needs to replace damaged cells with healthy new ones...and mitosis plays a crucial role in this process! Mitosis is a process of cell division that helps you stay alive and healthy. In other words, in the world of cell biology, mitosis is kind of a big deal!
But like with anything science-related, mitosis can be sort of confusing when you first try to understand it. The key idea is that the process of mitosis involves four phases , or steps, that you need to understand if you want to understand how mitosis works.
In this article, we’re going to do the following things to break down the four steps of mitosis for you and help you get acquainted with the mitosis phases:
- Briefly define mitosis and eukaryotic cells
- Break down the four phases of mitosis, in order
- Provide mitosis diagrams for the stages of mitosis
- Give you five resources for learning more about the phases of mitosis
Now, let’s dive in!
Feature image: Jpablo cad and Juliana Osorio/ Wikimedia Commons
(Marek Kultys/ Wikimedia Commons)
What Is Mitosis?
Mitosis is a process that occurs during the cell cycle . The role of mitosis in the cell cycle is to replicate the genetic material in an existing cell—known as the “parent cell”—and distribute that genetic material to two new cells, known as “daughter cells.” In order to pass its genetic material to the two new daughter cells, a parent cell must undergo cell division, or mitosis. Mitosis results in two new nuclei—which contain DNA—that eventually become two identical cells during cytokinesis .
Mitosis occurs in eukaryotic (animal) cells . Eukaryotic cells have a nucleus that contains the cell’s genetic material. A crucial part of mitosis involves breaking down the nuclear membrane that surrounds the cell’s DNA so that the DNA can be replicated and separated into new cells. Other types of cells, like prokaryotes , don’t have a nuclear membrane surrounding their cellular DNA, which is why mitosis only occurs in eukaryotic cells.
The main purpose of mitosis is to accomplish cell regeneration, cell replacement, and growth in living organisms . Mitosis is important because it ensures that all new cells that are generated in a given organism will have the same number of chromosomes and genetic information. In order to accomplish this goal, mitosis occurs in four discrete, consistently consecutive phases: 1) prophase, 2) metaphase, 3) anaphase, and 4) telophase .
We have an overview of mitosis here, which is more of an intro to what mitosis is and how it works . If you're a little shaky on mitosis still, that's definitely where you should start.
What we'll focus on in more detail in this article are the 4 stages of mitosis: prophase, metaphase, anaphase, telophase, and what happens during those phases! So let’s get down to it.
The 4 Phases of Mitosis: Prophase, Metaphase, Anaphase, Telophase
So what are the stages of mitosis? The four stages of mitosis are known as prophase, metaphase, anaphase, telophase. Additionally, we’ll mention three other intermediary stages (interphase, prometaphase, and cytokinesis) that play a role in mitosis.
During the four phases of mitosis, nuclear division occurs in order for one cell to split into two. Sounds simple enough, right? But different things occur in each step of mitosis, and each step is crucial to cell division occurring properly. That means successful cell division depends on the precision and regulation of each phase of mitosis. That’s why it’s important to be able to understand and articulate the role of each phase in mitosis overall.
Also: you may have seen or heard the parts of mitosis called different things: mitosis phases, the stages of mitosis, the steps of mitosis, or maybe even something else. All of those different phrases refer to the exact same process. As long as you remember that the phases/stages/steps of mitosis always happen in the same order, it doesn’t really matter which of those phrases you use!
Next, we’re going to breakdown the four phases of mitosis in order so you can understand how mitosis occurs through each phase.
(Ph. Immel/ Wikimedia Commons)
Interphase: What Happens Before Mitosis
We can think of interphase as a transitional phase. Interphase is when the parent cell prepares itself for mitosis . This phase isn’t considered part of mitosis, but understanding what happens during interphase can help the steps of mitosis make a little more sense.
You can think of interphase kind of like the opening act. They aren’t the band you came to see, but they get the audience warmed up for the main event.
I nterphase occurs prior to the beginning of mitosis and encompasses what’s called stage G1, or first gap, stage S, or synthesis, and stage G2, or second gap . Stages G1, S, and G2 must always occur in this order. The cell cycle begins with stage G1, which is a part of interphase.
So how does the parent cell prep itself for mitosis during interphase? During interphase, the cell is busy growing . It’s producing proteins and cytoplasmic organelles during the G1 phase, duplicating its chromosomes during the S phase, then continuing to grow in preparation for mitosis in the G2 phase.
In the cell cycle, interphase doesn’t just occur before mitosis—it also alternates with mitosis . It’s important to remember that this is a recurring cycle . When mitosis ends, interphase starts up again! In fact, in the grand scheme of the cell cycle, mitosis is a much shorter phase than interphase.
(Kelvinsong/ Wikimedia Commons )
Phase 1: Prophase
Prophase is the first step of mitosis. This is when the genetic fibers within the cell’s nucleus, known as chromatin , begin to condense and become tightly compacted together .
During interphase, the parent cell’s chromosomes are replicated, but they aren’t yet visible. They’re just floating around in the form of loosely collected chromatin. During prophase, that loose chromatin condenses and forms into visible, individual chromosomes.
Since each of the parent cell’s chromosomes were replicated during interphase, there are two copies of each chromosome in the cell during prophase. Once the chromatin has condensed into individual chromosomes, the genetically-identical chromosomes come together to form an “X” shape, called sister chromatids .
These sister chromatids carry identical DNA and are joined at the center (in the middle of the “X” shape) at a point called the centromere . The centromeres will serve as anchors that’ll be used to pull the sister chromatids apart during a later phase of mitosis. And that’s what’s happening inside the nucleus during prophase!
After the sister chromatids form, two structures called centrosomes move away from each other outside of the nucleus. As they move to opposite sides of the cell, the centrosomes form something called the mitotic spindle . The mitotic spindle will eventually be responsible for separating the identical sister chromatids into two new cells and is made up of long protein strands, called microtubules .
Late Prophase: Prometaphase
Prometaphase is often referred to as “late prophase.” (Though it’s also sometimes called “early metaphase” or referred to as a distinct phase entirely!) Regardless, some really important things occur during prometaphase that propel cell division along and that help explain what happens in metaphase.
Prometaphase is the phase of mitosis following prophase and preceding metaphase. The short version of what happens during prometaphase is that the nuclear membrane breaks down .
Here’s the long version of what happens during prometaphase: first, the nuclear membrane or nuclear envelope (i.e. the lipid bilayer surrounding the nucleus and encasing the genetic material in the nucleus) breaks apart into a bunch of membrane vesicles. Once the nuclear envelope breaks apart, the sister chromatids that were stuck inside the nucleus break free.
Now that the nucleus’s protective covering is gone, kinetochore microtubules move near the sister chromatids and attach to them at the centromere (that spot at the center of the “X”). Now these kinetochore microtubules are anchored at opposite poles on either end of the cell, so they’re extending themselves toward the sister chromatids and connecting them to one of the edges of the cell.
It’s kind of like catching a fish with a fishing pole—eventually, the chromatids are going to be separated and drawn to opposite ends of the cell.
And that’s the end of prometaphase. After prometaphase ends, metaphase—the second official phase of mitosis—begins.
Phase 2: Metaphase
Metaphase is the phase of mitosis that follows prophase and prometaphase and precedes anaphase. Metaphase begins once all the kinetochore microtubules get attached to the sister chromatids’ centromeres during prometaphase.
So here’s how it happens: the force generated during prometaphase causes the microtubules to start pulling back and forth on the sister chromatids. Since the microtubules are anchored at opposite ends of the cell, their back-and-forth pulling on different sides of the sister chromatids gradually shifts the sister chromatids to the middle of the cell.
This equal and opposite tension causes the sister chromatids to align along an imaginary—but very important!—line trailing down the middle of the cell. This imaginary line dividing the cell down the middle is called the metaphase plate or equatorial plane .
Now, in order for metaphase to progress on to anaphase, the sister chromatids must be equitably distributed across that metaphase plate. That’s where the metaphase checkpoint comes in: the metaphase checkpoint ensures that the kinetochores are properly attached to the mitotic spindles and that the sister chromatids are evenly distributed and aligned across the metaphase plate. If they are, the cell gets the green light to move on to the next phase of mitosis.
The checkpoint is very important because it helps the cell make sure that it mitosis will result in two new, identical cells with the same DNA! Only once the cell passes the metaphase checkpoint successfully can the cell proceed to the next stage of mitosis: anaphase.
Phase 3: Anaphase
The third phase of mitosis, following metaphase and preceding telophase, is anaphase. Since the sister chromatids began attaching to centrosomes on opposite ends of the cell in metaphase, they’re prepped and ready to start separating and forming genetically-identical daughter chromosomes during anaphase.
During anaphase, the centromeres at the center of the sister chromatids are severed . (It sounds worse than it is!) Remember how the sister chromatids are attached to the mitotic spindle? The spindle is made up of microtubules, which start shrinking during this phase of mitosis. They gradually pull the severed sister chromatids toward opposite poles of the cell.
Anaphase ensures that each chromosome receives identical copies of the parent cell’s DNA. The sister chromatids split apart down the middle at their centromere and become individual, identical chromosomes. Once the sister chromatids split during anaphase, they’re called sister chromosomes. (They’re actually more like identical twins!) These chromosomes will function independently in new, separate cells once mitosis is complete, but they still share identical genetic information.
Finally, during the second half of anaphase, the cell begins to elongate as polar microtubules push against each other . It goes from looking like one round cell to...well, more like an egg as the new chromosome sets pull further away from each other.
At the end of anaphase, chromosomes reach their maximum condensation level. This helps the newly separated chromosomes stay separated and prepares the nucleus to re-form . . . which occurs in the final phase of mitosis: telophase.
Phase 4: Telophase
Telophase is the last phase of mitosis. Telophase is when the newly separated daughter chromosomes get their own individual nuclear membranes and identical sets of chromosomes.
Toward the end of anaphase, the microtubules began pushing against each other and causing the cell to elongate. Those polar microtubules keep elongating the cell during telophase! In the meantime, the separated daughter chromosomes that are being pulled to opposite ends of the cell finally arrive at the mitotic spindle.
Once the daughter chromosomes have fully separated to opposite poles of the cell, the membrane vesicles of the parent cell’s old, broken down nuclear envelope form into a new nuclear envelope. This new nuclear envelope forms around the two sets of separated daughter chromosomes, creating two separate nuclei inside the same cell.
You might think of the events of telophase as a reversal of the events that occur during prophase and prometaphase. Remember how prophase and prometaphase are all about the nucleus of the parent cell starting to break down and separate? Telophase is about the reformation of the nuclear envelope around new nuclei to separate them from each cell’s cytoplasm.
Now that the two sets of daughter chromosomes are encased in a new nuclear envelope, they begin to spread out again . When this occurs, it is the end of telophase, and mitosis is complete.
(LadyofHats/ Wikimedia Commons )
Cytokinesis: What Happens After Mitosis
Like interphase, cytokinesis isn’t a part of mitosis, but it’s definitely an important part of the cell cycle that is essential to completing cell division. Sometimes, the occurrence of the events of cytokinesis overlaps with telophase and even anaphase, but cytokinesis is still considered a separate process from mitosis.
Cytokinesis is the actual division of the cell membrane into two discrete cells . At the end of mitosis, there are two new nuclei contained within the existing parent cell, which has stretched out into an oblong shape. So at this point, there’s actually two complete nuclei hanging out in one cell!
So how does one cell become two cells? Cytokinesis is responsible for completing the process of cell division by taking those new nuclei, separating the old cell in half, and ensuring that each of the new daughter cells contains one of the new nuclei.
Here’s how the separation of the old cell is accomplished during cytokinesis: remember that imaginary line running down the middle of the cell and dividing the centrosomes, called the metaphase plate? During cytokinesis, a contractile ring made of protein filaments develops where that metaphase plate used to be.
Once the contractile ring forms down the middle of the cell, it starts shrinking, which pulls the cell’s outer plasma membrane inward. You can think of it like a belt that just keeps tightening around the middle of the cell, squeezing it into two sections. Eventually, the contractile ring shrinks so much that the plasma membrane pinches off and the separated nuclei are able to form into their own cells.
The end of cytokinesis signifies the end of the M-phase of the cell cycle, of which mitosis is also a part. At the end of cytokinesis, the division part of the cell cycle has officially ended.
5 (Free!) Resources for Further Study of the Steps of Mitosis
Mitosis is a complex process, and the mitosis phases involve a lot of big words and unfamiliar concepts that you might want to learn more about. If you’re interested in diving more deeply into the 4 stages of mitosis, take a look at our five suggested resources for further study of the steps of mitosis, explained below!
#1: Mitosis Animations Online
Reading all about mitosis can definitely be helpful, but what if visuals really help you understand how things work? That’s where web animations of mitosis might come in handy for you. Watching mitosis in action through web animations can help give you an idea of what all those verbal descriptions really mean. They can also help you picture what the phases of mitosis might look like under a real microscope!
There are probably a lot of web animations of mitosis that you could take a look at, but we recommend these three:
- John Kyrk’s Mitosis Animation
- The Biology Project’s “Online Onion Root Tips”
- Cells Alive’s “Animal Cell Mitosis”
We particularly like Cells Alive’s “Animal Cell Mitosis” animation because it allows you to pause the animation as it loops through the phases of mitosis in order to take a fine-grained look at how mitosis works. Cells Alive’s version also juxtaposes its animation of the mitosis phases with footage of mitosis occurring under a microscope, so you’ll know what you’re looking for if you’re ever tasked with observing cell mitosis in the lab.
#2: “ Mitosis: Splitting Up Is Hard To Do ” by Crash Course
If you’re a bit exhausted from reading dense material and need someone else to put the stages of mitosis into more accessible terms, head over to YouTube and watch Crash Course’s 10 minute video on mitosis, called “Mitosis: Splitting Up Is Hard to Do.”
The nice thing about this video is that, while being a bit more thorough than some of the other YouTube videos you might find out there on mitosis, it’s also really funny. More importantly, it explains mitosis in terms of familiar, everyday biological processes , like when you get a cut and need your body to make new cells to heal.
If you need help thinking about the real-world relevance of the mitosis phases beyond just being something you have to memorize for a lab or exam, this is a great resource.
#3: “ Phases of Mitosis ” by Khan Academy
Here’s another YouTube video, but the tone and style of this explanation of the steps of mitosis by Khan Academy is a little different. Watching this tutorial on the mitosis phases feels a bit like you’re sitting in biology class and your teacher/professor is drawing out diagrams of mitosis while talking you through the entire process (except in this case, your teacher is sort of cool and only uses neon colors to draw the diagrams).
If you’re looking for a step-by-step tutorial that takes a slow pace and deals with the steps of mitosis thoroughly, Khan Academy has you covered!
#4: Creating a Mitosis Flip Book
For some learners, the process of creating something to show your knowledge can help with memorization of difficult concepts and/or developing a thorough understanding of how things work. That’s why we suggest trying out some old-school tactics to build your knowledge of the 4 stages of mitosis! A tried-and-true approach to learning the mitosis phases, vetted by biology teachers, is creating a mitosis flip book.
Post-It provides a step-by-step guide on how you can create a mitosis flip book on your own, but it’s really pretty simple: you get something to draw with, grab small note cards or sticky notes to draw on, and draw what each phase of the cell cycle looks like on individual note cards/sticky notes!
When you’ve finished drawing your version of the stages of mitosis on your cards, you either stick, tape, or staple them together, and voila! You can flip through your mitosis flip book from beginning to end and watch the progression of mitosis through the four phases.
Activities like this one can help imprint on your memory what each step of mitosis looks like. Plus, when you finish your flip book, you’ve got a pocket-sized resource that you can carry with you as a part of your study guide or a quick resource for review before a quiz or exam!
#5: “ Mitosis Study Set ” by ProProfs Flashcards
Maybe you’re feeling pretty good about your knowledge of the stages of mitosis but you want some help in testing that knowledge before a formal quiz or exam. That’s where ProProfs Flashcards’ “Mitosis Study Set,” an online study guide that provides an array of flashcards to help you test your knowledge of the stages of mitosis, comes in.
What’s fun about this flashcard set is that you can choose different assessment styles depending on where you are in your knowledge of mitosis. The flashcard set provides traditional question-and-answer flashcards, a flashcard function specifically geared toward memorization, a multiple choice quiz, and matching. If you want to practice being tested on the steps of mitosis before the actual test, check out this resource!
ProProfs Flashcards provides several study sets on other topics related to or involving mitosis, so if you need to test your knowledge of mitosis beyond just the four phases, this resource could help out there as well.
What's the difference between mitosis and meiosis ? Learn more with our side-by-side comparison.
Need to review the different parts of the cell and what they do? We walk you through the functions of the cell membrane , endoplasmic reticulum , and vacuoles . If you learn better by looking at the big picture, you'll also want to keep our complete guide to animal cells handy so you can refer back to it while reading about each individual cell structure.
If you want more traditional resources to help you learn about the cell cycle, our list of the best AP Biology books for studying has you covered .
Taking science classes in high school (and doing well in them!) is an important step on your journey to get into the university of your dreams. Check out this article about which science classes you need to take before applying for college to figure out which classes are right for you.
Need more help with this topic? Check out Tutorbase!
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Ashley Sufflé Robinson has a Ph.D. in 19th Century English Literature. As a content writer for PrepScholar, Ashley is passionate about giving college-bound students the in-depth information they need to get into the school of their dreams.
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In biology, mitosis is the process by which a cell separates its duplicated genome into two identical halves.
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How to Write a News Article
News articles report on current events that are relevant to the readership of a publication. These current events might take place locally, nationally, or internationally.
News writing is a skill that’s used worldwide, but this writing format—with its unique rules and structure—differs from other forms of writing . Understanding how to write a news story correctly can ensure you’re performing your journalistic duty to your audience.
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What is a news article?
A news article is a writing format that provides concise and factual information to a reader. News stories typically report on current affairs that are noteworthy—including legislation, announcements, education, discoveries or research, election results, public health, sports, and the arts.
Unlike blog and opinion posts, a strong news article doesn’t include personal opinion, speculation, or bias. Additionally, the diction and syntax should be accessible to any reader, even if they’re not deeply familiar with the topic. News stories, therefore, don’t contain jargon that you might find in a research paper or essay.
What are the rules for writing a news article?
Whether you’re learning how to write a short news story for a school assignment or want to showcase a variety of clips in your writing portfolio , the rules of news writing hold true.
There are three types of news articles:
- Local: reports on current events of a specific area or community. For example, “College Football Team Welcomes Legendary NFL Coach” or “School District Announces New Grading Policy.”
- National: reports on current affairs within a particular country. For example, “NASA’s James Webb Telescope Captures Surreal Images of the Cosmos.”
- International: reports on social issues or current affairs of one or more countries abroad. For example, “UK’s Record Heat Wave Expected to Continue Next Week.”
Regardless of the type of news article you’re writing, it should always include the facts of the story, a catchy but informative headline, a summary of events in paragraph form, and interview quotes from expert sources or of public sentiment about the event. News stories are typically written from a third-person point of view while avoiding opinion, speculation, or an informal tone.
How is a news article structured?
While many news stories are concise and straightforward, long-form or deeply investigated pieces may comprise thousands of words. On the shorter side, news articles can be about 500 words.
When it comes to how to structure a news article, use an inverted pyramid. Organizing your content this way allows you to thoughtfully structure paragraphs :
- Begin with the most important and timely information
- Follow those facts with supporting details
- Conclude with some less important—but relevant—details, interview quotes, and a summary
The first paragraph of a news article should begin with a topic sentence that concisely describes the main point of the story. Placing this sentence at the beginning of a news article hooks the reader immediately so the lede isn’t buried.
At a traditional newspaper, this practice is described as “writing above the fold,” which alludes to the biggest, most pressing news being visible at the top of a folded newspaper.
How to write a news article
There are a handful of steps to practice when writing a news story. Here’s how to approach it.
1 Gathering information
Source the five Ws about your news topic: who, what, where, when, and why. Lock down a keen understanding of the timeline of events so you can correctly summarize the incident or news to your reader. The key is to position yourself as a credible and reliable source of information by doing your due diligence as a fact gatherer.
2 Interviewing subjects
Consider who you want to interview for the new article. For example, you might choose to interview primary sources , such as a person who is directly involved in the story.
Alternatively, secondary sources might offer your readers insight from people close to or affected by the topic who have unique perspectives. This might be an expert who can offer technical commentary or analysis, or an everyday person who can share an anecdote about how the topic affected them.
When interviewing sources, always disclose that you’re a reporter and the topic that you’re writing on.
Draft an outline for your news article, keeping the inverted-pyramid structure in mind. Consider your potential readership and publication to ensure that your writing meets the audience’s expectations in terms of complexity.
For example, if this news article is for a general news publication, your readership might include a wider audience compared to a news article for a specialized publication or community.
Brainstorm a snappy headline that concisely informs readers of the news topic while seizing their interest. Gather the most important points from your research and pool them into their respective pyramid “buckets.” These buckets should be based on their order of importance.
Get to writing! The paragraphs in a news article should be short, to the point, and written in a formal tone. Make sure that any statements or opinions are attributed to a credible source that you’ve vetted.
Reread your first draft aloud. In addition to looking for obvious typos or grammar mistakes , listen for awkward transitions and jarring tense or perspective shifts. Also, consider whether your first draft successfully conveys the purpose of your news story.
Rework your writing as needed and repeat this step. Don’t forget to proofread your work.
Strong news stories are built on facts. If any statement or information is shaky or unsupported, the entire work is compromised. Before publishing a news article, double-check that all the information you’ve gathered from the beginning is accurate, and validate the information that your interview sources provided, too.
How to write a news article FAQs
What is a news article .
A news article informs readers within a community of current events that are relevant to them. It typically revolves around a topic of interest within a publication’s readership, whether the information is about local, national, or international events.
News articles are structured like an inverted pyramid. The most important or crucial information is always presented to the reader up front, followed by additional story details. A news article concludes with less important supporting information or a summation of the reporting.
The general rules for writing a news article involve accuracy and integrity. Report on the details of a story in a factual, unbiased, and straightforward way. When writing a news article, do not editorialize or sensationalize the information, and keep your content free of your opinion.
To revist this article, visit My Profile, then View saved stories .
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How to Use Obsidian for Writing and Productivity
I'm pretty bad at being an employee. I openly despise meetings, I say exactly what's on my mind, and I sincerely believe that many managers exist only to waste the time of otherwise productive people. I also could not be less interested in how my work impacts quarterly projections—I want to write things that people find helpful and entertaining.
So, yeah, I'm a freelancer.
I write for five publications, including the one you're reading now (obviously my favorite). The upside: I'm never in meetings. The downside: There's a lot to keep track of. I have to manage relationships with five editors. It's a challenge, and I've tried a full array of systems over the years, from spreadsheets to index cards, apps like Trello , and way too many to-do list apps.
None of them quite did the trick, until I discovered Obsidian a couple of years ago. This application has slowly gone from being a weird app I didn't understand to one I can't imagine functioning without. It's where I do all of my writing, yes, but also how I keep track of my ongoing articles as they move from brainstorming to pitching to publication.
This isn't a review of Obsidian ( I already wrote one ). This is an outline of how I use this tool to get things done. Hopefully reading it gives you some ideas for how you could use it.
First of all, what is Obsidian? The application bills itself as a "second brain," but you could it put in the same category as note-taking apps like OneNote or Evernote. Unlike those applications, though, Obsidian stores everything—notes, attachments, and even plugins—as simple text documents in a folder on your computer. This means you can use the application fully offline or sync the documents using the cloud storage service of your choice.
This has a few advantages. For one, your files are fully in your control: If Obsidian stopped existing tomorrow, I would still have access to my notes. For another, everything works offline. My favorite thing about Obsidian, though, is the extensive plugin ecosystem. There are over a thousand Obsidian plugins , and I depend on several of them. There's Kanban , which allows you to create a board of cards you can move between tiles. There's Extract URL , which can grab all text from any website and turn it into a note. I could list plugins for a long time. But the point is that you can customize Obsidian to work basically any way you want it to. I've done this to create a perfect setup for my workflow—one that allows me to do my planning and my actual writing in the same application.
My writing process has a progression: brainstorming ideas, pitching those ideas to editors, researching, writing, editing, and invoicing. Here's how I move through these steps in Obsidian.
Every article starts with an idea. I get these from all kinds of places. Sometimes I'm just using my computer, notice something that annoys me, endlessly research a solution to that issue, and then decide to write about it. Sometimes I notice a cool-looking app while reading the news or browsing Reddit. And sometimes I just spend a few hours brainstorming ideas. Whatever the case, I compile my ideas in a dedicated Kanban board on Obsidian. Every card on the board links to a dedicated document where I include any relevant links, expand on the idea, and note a bit about possible angles for the article.
When it comes time to take these ideas into the world, I decide which ones I'm going to pitch to which editors and drag them to a column for that publication. If the pitch is approved, I drag the card over to my "article queue" board, if not, I consider pitching it to another publication or put it in my "idea jail" to potentially revisit later.
I like this system because it allows me to slowly collect ideas throughout the month. That way, when it comes time to pitch, I'm not starting from scratch.
The core of my workflow is the "article queue" Kanban board, which basically contains every article I'm working on in the current month. I have a column for every step of the editorial process—writing, waiting on edits, editing, edited but not invoiced, invoiced but not paid, and paid. I drag articles from left to right.
I live by this board. Every work day I log in, look at how far along I am with every article, and decide what to work on. The board also means I never forget to follow up with editors who might have forgotten to email me feedback, or to follow up on unpaid invoices. I sincerely don't know how I functioned before I had this.
Even better, this isn't just a project management system: It's also the app where I do my writing. I can click any of these cards and start writing, right away. I can't overstate how helpful it is to not have to use one application for project management and another for the writing itself.
Obsidian is a great place for writing. Formatting is handled by Markdown , a simple way to apply formatting—for example, to bold text you surround it with two asterisks, **like this**. I've done all of my writing in Markdown for a long time, so this is perfect for me.
Some Markdown editors use two panels—one where you write, with the formatting “code” visible, and another where you preview how the text will look. Obsidian doesn't do this, opting to render the Markdown in real time as you type. This is a perfect compromise—it gives me the benefit of writing in Markdown without the downside of my text editor looking ugly as sin. This is a feature I first saw in an app called Typora , and I'm glad it works here too.
I write a lot of tech tutorials, and I generally start by collecting screenshots for every step. I put all of the screenshots, in order, in a document in Obsidian, along with all of the relevant links. If I'm doing a reported piece, I gather my research and interviews in separate documents, then compile the best quotes and tidbits into the document where I'll do my writing. Obsidian offers an internal linking feature—it can basically function as a private wiki—and I use this to connect all of my interviews and other research to my article for tracking purposes. It's possible to view multiple documents in the same window, a feature I use all the time.
The Canvas feature, which is relatively new, offers a way to arrange and edit multiple documents in the same place—I personally don't use this, but I can see the appeal of dragging documents wherever you like and editing them all in one interface.
Obsidian doesn't really have any collaboration features, and even if it did my editors don't use it. That's why I use a plugin called Copy as HTML to copy a rich text version of my article. I paste this into a Google Doc, which renders it as formatted text, complete with images. I share this with my editors, all of whom use comments and track changes to give me feedback.
That, in a nutshell, is how I manage to pitch, write, and track 15 to 20 articles between five different editors every month. It's a lot of work, granted, but I enjoy it. And this workflow makes it all feel manageable.
I can't imagine that this exact process would work for most of you, and that's not the point. Obsidian is useful because you can adapt it to almost any workflow, no matter how specific your needs are. I spent a lot of time customizing everything so it works just so; you can do the same thing. Other apps try to get you to adapt to a particular way of working. Obsidian, if you put the time in, will adapt to you.
WIRED has teamed up with Jobbio to create WIRED Hired , a dedicated career marketplace for WIRED readers. Companies who want to advertise their jobs can visit WIRED Hired to post open roles, while anyone can search and apply for thousands of career opportunities. Jobbio is not involved with this story or any editorial content.
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A Giant Inland Sea Is Now a Desert, and a Warning for Humanity
By Jacob Dreyer
Mr. Dreyer, an editor and writer, wrote from Muynak, Uzbekistan.
Walking toward the shrinking remnants of what used to be the Aral Sea in Uzbekistan was like entering hell.
All around was a desert devoid of life, aside from scrubby saxaul trees. Dust swirled in 110-degree Fahrenheit heat under a throbbing red sun. I reached the edge of one of the scattered lakes that are all that remain of this once-great body of water. I took off my shoes and waded in. The water was so full of salt that it felt viscous, not quite liquid.
In the nearby town of Muynak, black-and-white newsreels in the local museum and pictures in the family photo albums of residents tell of better times. During the Soviet era, fishing communities like Muynak ringed the sea, thriving off its bounty: sturgeon, flounder, caviar and other staples of Soviet dinner tables. In the town I met Oktyabr Dospanov, an archaeologist who grew up along the Aral’s shores and recalls a “happy life” in his youth, when fishing boats, passenger ships and cargo trawlers plied the sea’s waves around the clock.
But over the decades, Soviet authorities diverted rivers that flowed into the sea to irrigate cotton and other crops. The world’s fourth-largest inland body of water — which covered an area about 15 percent larger than Lake Michigan — gradually shrank, triggering a domino effect of ecological, economic and community collapse, the kind of catastrophe that could befall other environmentally fragile parts of the world unless we change our ways.
By 2007, the sea’s surface area had shrunk by around 90 percent , leaving Muynak a landlocked way station for tourists who come to marvel at this ecological disaster, where they take selfies near rusting ship hulks that are perched high and dry in the endless sand.
Although restoration efforts in recent years have led to small improvements in some areas, the former expanse of the Aral Sea is a blighted realm, where a scattering of far smaller, brackish lakes lie like puddles in a vast dry basin. The Aral Sea is now the Aralkum Desert. Over the decades, soil and water were contaminated by pesticides and other pollutants, which are suspected of causing birth defects and other chronic health problems in the area.
As the Aral Sea died, the region’s once-rich pastures and forests began to degrade, according to Mr. Dospanov. Birds, insects and other wildlife that depend on the sea and its wider environment disappeared. It was as if without the sea, biodiversity went into freefall.
Salty dust blown from the parched seabed has severely affected crops. Other livelihoods tied to the sea have also suffered, and over the decades local incomes fell and unemployment rose. The population of the region dropped as people migrated to the Uzbek capital, Tashkent, or to Moscow, where many work in construction or other low-paying jobs and often face discrimination . An entire natural and human ecosystem was destroyed. Worse, the Soviet authorities knew what was happening , but priorities like economic growth seemed more important. By the 1980s, authorities even considered compounding the folly by diverting water from Lake Baikal in Siberia, more than 2,000 miles away, to the Aral region. The Soviet Union collapsed before that scheme could be carried out.
Last year, protests broke out in Karakalpakstan, the region where the Aral Sea was, after a proposal by the government of Uzbekistan that would have reduced the region’s autonomy. Many observers have noted that economic and environmental hardship related to the sea’s demise have added to the region’s volatility.
The really scary thing about the Aral Sea is that environmental catastrophes like it are being replicated across the world. We see refugees fleeing from uninhabitable homelands, bitter conflicts over scarce resources and land, and cities threatened by rising sea levels.
In the United States, Lake Mead and the Great Salt Lake are shrinking, and cities like Los Angeles are racing to balance their water needs with a changing climate. Agriculture, fracking, lawn maintenance and other activities are rapidly depleting groundwater aquifers across America. Can we live with the possibility that other places are headed for a fate similar to the Aral Sea’s? The human race is using up its water and other resources like there’s no tomorrow, but as the residents of Muynak found out, there was a tomorrow, just not the one they were hoping for.
For Mr. Dospanov, the sea was a microcosm of humanity’s deep economic and social connection to the environment. A culture and a way of life blossomed around the Aral Sea, in symbiosis with it, dependent upon it. But the sea’s destruction caused everything else to collapse along with it, he said.
I left for Tashkent to catch a flight back to China, where I live, eager to leave Karakalpakstan behind. But I would have to wait: Beijing had been hit by the heaviest rains in years (prompting discussion of whether climate change was partly to blame), stranding me for a while in Tashkent.
The Aral Sea stands as a grim parable, a warning of what can come from humanity’s environmental hubris. If we continue this way, waiting for somebody else to do something or letting short-term economic interests stand in the way , we may find ourselves like Mr. Dospanov, telling visitors about how beautiful our home once was.
Jacob Dreyer is an editor and writer who lives in Shanghai.
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LinkedIn has AI to enhance profiles. It made some sound robotic.
Linkedin’s new ai feature aims to help users market themselves better on the job website by offering profile recommendations.
If you’re one of the many users who struggle to tell your professional story on the job site LinkedIn, a built-in artificial intelligence tool may now offer some assistance. But whether using AI is worth your time may depend on how creative you want your profile to be.
LinkedIn began rolling out a generative AI feature to select users this spring, powered by OpenAI’s GPT-4 model, to help premium subscribers write headlines and “about” sections. Users can generate text summarizing what’s already in their profile and get spruced-up suggestions offered by the feature, which is highlighted with a gold button that says “write with AI.” The capability is available to all of LinkedIn’s millions of premium subscribers, and the company said it’s exploring expanding access in the future.
Generative AI features have been making their way into services and products across industries ever since OpenAI made a big splash with its AI bot ChatGPT late last year. Since then, Microsoft, a big investor in OpenAI, Google and others have been debuting new generative AI features across their product lines. LinkedIn, which is owned by Microsoft, is joining the bunch with its latest rollout.
The Help Desk tried this feature and talked to some users about their experience, and they generally had the same impression: Though the AI suggestions may help you get started, they are too cookie-cutter and sometimes not factually correct.
“It just feels lifeless,” said Pete DeOlympio, marketing director at AI and data analytics consulting firm Cleartelligence in Newton, Mass. “And the [AI-generated] version I got is technically wrong.”
LinkedIn says about 70 percent of users who try the AI feature apply the recommended suggestions — either as is or with a few tweaks. The company also said it recognizes AI sometimes gets things wrong, and it is working to reduce errors. It recommends that anyone who uses the tool review the suggestions for accuracy and edit if needed. If the AI-generated suggestions feel too robotic, users can tweak their original profile and then rerun the tool to get variations. The company is still working on improving tone.
“Our AI powered suggestions … are personalized by members,” based on what’s on their profiles, said Laura Teclemariam, senior director of product at LinkedIn. “We believe [the suggestions] will get better over time.”
LinkedIn also said it is testing and rolling out other new AI capabilities that allow users to see personalized summaries of their feeds, write posts and messages and better connect to jobs for which they might be a good fit. And it has been coupling AI-generated conversation-starters with member insights to publish what it calls “collaborative articles” on topics such as leadership, team building and other skills.
Use AI critically
After testing the profile feature at the Help Desk, a couple of key things stood out. First, users need to ensure their profile is filled out for the AI to accurately pull titles and background. Otherwise it will pull whatever is there, which may not be the most relevant items to highlight up top. Second, like most generative AI, the output might be a little wordy (the content was nearly doubled in one case) and a little generic — so consider editing.
In one test, the headline offered multiple options but the about section only offered one. It also stripped out some items that may not necessarily pertain to a user’s professional journey but rather offer some insight to quirks or insights to their personality.
DeOlympio said that the tool might be useful for people who need help drafting something for their profile, but said it introduced an error when it assumed he oversaw a team. It also felt too bland for his personality.
Several other users agreed.
“The AI stripped the hook I had,” said Morgan Short, St. Paul, Minn.-based director of content and web strategy at price-management software company Vendavo, adding that some suggestions also created redundancy. “It can’t show the narrative if you’re trying to create a brand that sets yourself apart.”
Some of the content the AI generates seemingly blends commonalities of a person’s job title with what’s actually in their profile to create the result, said Donna Svei, an executive resume writer in Los Angeles. And it may not be great for optimizing your profile for career advancement or changes, she said. That’s because the AI may summarize the experience and titles you already have versus what you aim to become.
“The first few words in your profile [like the headline] have more [search] weight than any other field,” she said, adding that the AI highlights only your current and previous roles. “But you need to use the title you want in your headline.”
For Sangeeta Krishnan, senior analytics lead at pharmaceutical and biotech company Bayer, the problem was the AI doesn’t allow users to customize what they want to highlight based on what’s most important in their industry. And in her case, the AI highlighted old certifications at the bottom of her list rather than elevating the more relevant ones she lists first in her profile. She also wished she could dial up or down different tones.
“Everyone’s style of writing is different,” she said. “Maybe you could ask it to make it more professional or make it more funny, but it only gives you one option.”
But as more people turn to AI for content, more text may start sounding the same, several users said. Svei said her brain clicks off when she reads items written by AI because it tends to be written in a way that makes the content less interesting. Short sees a lot of value in both generative AI and LinkedIn, but she wouldn’t recommend it for enhancing your profile.
“I highly recommend optimizing your LinkedIn profile, but use the AI critically,” she said. “It’s a tool like anything else.”
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