After cytokinesis how does the number of chromosomes

Although Flemming was able to correctly deduce the sequence of events in mitosis, this sequence could not be experimentally verified for several decades, until advances in light microscopy made it possible to observe chromosome movements in living cells. Researchers now know that mitosis is a highly regulated process involving hundreds of different cellular proteins.

The dynamic nature of mitosis is best appreciated when this process is viewed in living cells. Figure 2 Figure 1 Figure Detail In his pioneering studies of mitosis, Flemming noted that the nuclear material, which he named " chromatin " for its ability to take up stains, did not have the same appearance in all cells.

We still use the word "chromatin" today, albeit in a more biochemical sense to refer to complexes of nuclear DNA and protein. Specifically, in some cells, chromatin appeared as an amorphous network, although in other cells, it appeared as threadlike bodies that Flemming named "mitosen.

Today, scientists know that Flemming had successfully distinguished chromosomes in the interphase portion of the cell cycle from chromosomes undergoing mitosis, or the portion of the cell cycle during which the nucleus divides Figure 1. With very few exceptions, mitosis occupies a much smaller fraction of the cell cycle than interphase.

The difference in DNA compaction between interphase and mitosis is dramatic. A precise estimate of the difference is not possible, but during interphase, chromatin may be hundreds or even thousands of times less condensed than it is during mitosis.

For this reason, the enzyme complexes that copy DNA have the greatest access to chromosomal DNA during interphase, at which time the vast majority of gene transcription occurs. In addition, chromosomal DNA is duplicated during a subportion of interphase known as the S, or synthesis, phase. As the two daughter DNA strands are produced from the chromosomal DNA during S phase , these daughter strands recruit additional histones and other proteins to form the structures known as sister chromatids Figure 2.

The sister chromatids, in turn, become "glued" together by a protein complex named cohesin. Cohesin is a member of the SMC, or structural maintenance of chromosomes, family of proteins. SMC proteins are DNA-binding proteins that affect chromosome architectures; indeed, cells that lack SMC proteins show a variety of defects in chromosome stability or chromosome behavior.

At the end of S phase, cells are able to sense whether their DNA has been successfully copied, using a complicated set of checkpoint controls that are still not fully understood. For the most part, only cells that have successfully copied their DNA will proceed into mitosis. The most obvious difference between interphase and mitosis involves the appearance of a cell 's chromosomes.

During interphase, individual chromosomes are not visible, and the chromatin appears diffuse and unorganized. Like cohesin, condensin is an elongated complex of several proteins that binds and encircles DNA. In contrast to cohesin, which binds two sister chromatids together, condensin is thought to bind a single chromatid at multiple spots, twisting the chromatin into a variety of coils and loops Figure 3. During mitosis, chromosomes become attached to the structure known as the mitotic spindle.

In the late s, Theodor Boveri created the earliest detailed drawings of the spindle based on his observations of cell division in early Ascaris embryos Figure 4; Satzinger, Boveri's drawings, which are amazingly accurate, show chromosomes attached to a bipolar network of fibers.

Boveri observed that the spindle fibers radiate from structures at each pole that we now recognize as centrosomes, and he also noted that each centrosome contains two small, rodlike bodies, which are now known as centrioles.

Boveri observed that the centrioles duplicate before the chromosomes become visible and that the two pairs of centrioles move to separate poles before the spindle assembles. We now know that centrioles duplicate during S phase, although many details of this duplication process are still under investigation. It is now well-established that spindles are bipolar arrays of microtubules composed of tubulin Figure 5 and that the centrosomes nucleate the growth of the spindle microtubules. During mitosis, many of the spindle fibers attach to chromosomes at their kinetochores Figure 6 , which are specialized structures in the most constricted regions of the chromosomes.

The length of these kinetochore-attached microtubules then decreases during mitosis, pulling sister chromatids to opposite poles of the spindle. Other spindle fibers do not attach to chromosomes, but instead form a scaffold that provides mechanical force to separate the daughter nuclei at the end of mitosis.

From his many detailed drawings of mitosen, Walther Flemming correctly deduced, but could not prove, the sequence of chromosome movements during mitosis Figure 7.

Flemming divided mitosis into two broad parts: a progressive phase, during which the chromosomes condensed and aligned at the center of the spindle, and a regressive phase, during which the sister chromatids separated. Our modern understanding of mitosis has benefited from advances in light microscopy that have allowed investigators to follow the process of mitosis in living cells.

Such live cell imaging not only confirms Flemming's observations, but it also reveals an extremely dynamic process that can only be partially appreciated in still images. Mitosis begins with prophase, during which chromosomes recruit condensin and begin to undergo a condensation process that will continue until metaphase. In most species , cohesin is largely removed from the arms of the sister chromatids during prophase, allowing the individual sister chromatids to be resolved.

Cohesin is retained, however, at the most constricted part of the chromosome, the centromere Figure 9. During prophase, the spindle also begins to form as the two pairs of centrioles move to opposite poles and microtubules begin to polymerize from the duplicated centrosomes. Prometaphase begins with the abrupt fragmentation of the nuclear envelope into many small vesicles that will eventually be divided between the future daughter cells.

The breakdown of the nuclear membrane is an essential step for spindle assembly. Because the centrosomes are located outside the nucleus in animal cells, the microtubules of the developing spindle do not have access to the chromosomes until the nuclear membrane breaks apart. Prometaphase is an extremely dynamic part of the cell cycle. Microtubules rapidly assemble and disassemble as they grow out of the centrosomes, seeking out attachment sites at chromosome kinetochores, which are complex platelike structures that assemble during prometaphase on one face of each sister chromatid at its centromere.

As prometaphase ensues, chromosomes are pulled and tugged in opposite directions by microtubules growing out from both poles of the spindle, until the pole-directed forces are finally balanced. Sister chromatids do not break apart during this tug-of-war because they are firmly attached to each other by the cohesin remaining at their centromeres. At the end of prometaphase, chromosomes have a bi-orientation, meaning that the kinetochores on sister chromatids are connected by microtubules to opposite poles of the spindle.

Next, chromosomes assume their most compacted state during metaphase, when the centromeres of all the cell's chromosomes line up at the equator of the spindle. Metaphase is particularly useful in cytogenetics , because chromosomes can be most easily visualized at this stage. Furthermore, cells can be experimentally arrested at metaphase with mitotic poisons such as colchicine.

Video microscopy shows that chromosomes temporarily stop moving during metaphase. A complex checkpoint mechanism determines whether the spindle is properly assembled, and for the most part, only cells with correctly assembled spindles enter anaphase. Figure 10 Figure Detail. Figure 9.

The progression of cells from metaphase into anaphase is marked by the abrupt separation of sister chromatids. A major reason for chromatid separation is the precipitous degradation of the cohesin molecules joining the sister chromatids by the protease separase Figure Two separate classes of movements occur during anaphase.

During the first part of anaphase, the kinetochore microtubules shorten, and the chromosomes move toward the spindle poles. During the second part of anaphase, the spindle poles separate as the non-kinetochore microtubules move past each other. These latter movements are currently thought to be catalyzed by motor proteins that connect microtubules with opposite polarity and then "walk" toward the end of the microtubules. Mitosis ends with telophase, or the stage at which the chromosomes reach the poles.

The nuclear membrane then reforms, and the chromosomes begin to decondense into their interphase conformations. Telophase is followed by cytokinesis, or the division of the cytoplasm into two daughter cells. The daughter cells that result from this process have identical genetic compositions. Cheeseman, I. Molecular architecture of the kinetochore-microtubule interface. Nature Reviews Molecular Cell Biology 9 , 33—46 doi Cremer, T.

Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature Reviews Genetics 2 , — doi Hagstrom, K. Condensin and cohesin: More than chromosome compactor and glue. Nature Reviews Genetics 4 , — doi Hirano, T. At the heart of the chromosome: SMC proteins in action.

Nature Reviews Molecular Cell Biology 7 , — doi Mitchison, T. Mitosis: A history of division. Nature Cell Biology 3 , E17—E21 doi Paweletz, N.

Walther Flemming: Pioneer of mitosis research. Nature Reviews Molecular Cell Biology 2 , 72—75 doi Satzinger, H.

Theodor and Marcella Boveri: Chromosomes and cytoplasm in heredity and development. Nature Reviews Genetics 9 , — doi Chromosome Mapping: Idiograms. Mitosis consists of five morphologically distinct phases: prophase, prometaphase, metaphase, anaphase, and telophase. Each phase involves characteristic steps in the process of chromosome alignment and separation.

Once mitosis is complete, the entire cell divides in two by way of the process called cytokinesis Figure 1. Walther Flemming: pioneer of mitosis research. Nature Reviews Molecular Cell Biology 2, 72 All rights reserved. Prophase is the first stage in mitosis, occurring after the conclusion of the G 2 portion of interphase. During prophase, the parent cell chromosomes — which were duplicated during S phase — condense and become thousands of times more compact than they were during interphase.

Because each duplicated chromosome consists of two identical sister chromatids joined at a point called the centromere , these structures now appear as X-shaped bodies when viewed under a microscope. Several DNA binding proteins catalyze the condensation process, including cohesin and condensin. Cohesin forms rings that hold the sister chromatids together, whereas condensin forms rings that coil the chromosomes into highly compact forms. The mitotic spindle also begins to develop during prophase.

As the cell's two centrosomes move toward opposite poles, microtubules gradually assemble between them, forming the network that will later pull the duplicated chromosomes apart. When prophase is complete, the cell enters prometaphase — the second stage of mitosis. During prometaphase, phosphorylation of nuclear lamins by M-CDK causes the nuclear membrane to break down into numerous small vesicles.

As a result, the spindle microtubules now have direct access to the genetic material of the cell. As prometaphase ends and metaphase begins, the chromosomes align along the cell equator. Every chromosome has at least two microtubules extending from its kinetochore — with at least one microtubule connected to each pole.

At this point, the tension within the cell becomes balanced, and the chromosomes no longer move back and forth. In addition, the spindle is now complete, and three groups of spindle microtubules are apparent. Kinetochore microtubules attach the chromosomes to the spindle pole; interpolar microtubules extend from the spindle pole across the equator, almost to the opposite spindle pole; and astral microtubules extend from the spindle pole to the cell membrane.

Metaphase leads to anaphase , during which each chromosome's sister chromatids separate and move to opposite poles of the cell. Enzymatic breakdown of cohesin — which linked the sister chromatids together during prophase — causes this separation to occur.

Upon separation, every chromatid becomes an independent chromosome. Meanwhile, changes in microtubule length provide the mechanism for chromosome movement. More specifically, in the first part of anaphase — sometimes called anaphase A — the kinetochore microtubules shorten and draw the chromosomes toward the spindle poles. Then, in the second part of anaphase — sometimes called anaphase B — the astral microtubules that are anchored to the cell membrane pull the poles further apart and the interpolar microtubules slide past each other, exerting additional pull on the chromosomes Figure 2.

Figure 2: Types of microtubules involved in mitosis During mitosis, several types of microtubules are active. The motor proteins associated with the interpolar microtubules drive the assembly of the spindle. Note the other types of microtubules involved in anchoring the spindle pole and pulling apart the sister chromatids. Figure Detail. Cytokinesis is the physical process that finally splits the parent cell into two identical daughter cells.

During cytokinesis, the cell membrane pinches in at the cell equator, forming a cleft called the cleavage furrow. The position of the furrow depends on the position of the astral and interpolar microtubules during anaphase. The cleavage furrow forms because of the action of a contractile ring of overlapping actin and myosin filaments.

As the actin and myosin filaments move past each other, the contractile ring becomes smaller, akin to pulling a drawstring at the top of a purse. When the ring reaches its smallest point, the cleavage furrow completely bisects the cell at its center, resulting in two separate daughter cells of equal size Figure 3.

Figure 3: Mitosis: Overview of major phases The major stages of mitosis are prophase top row , metaphase and anaphase middle row , and telophase bottom row. This page appears in the following eBook. Aa Aa Aa. What Are the Phases of Mitosis? Figure 1: Drawing of chromosomes during mitosis by Walther Flemming, circa What Happens during Prophase?

What Happens during Prometaphase? Each microtubule is highly dynamic, growing outward from the centrosome and collapsing backward as it tries to locate a chromosome. Eventually, the microtubules find their targets and connect to each chromosome at its kinetochore , a complex of proteins positioned at the centromere.

The actual number of microtubules that attach to a kinetochore varies between species, but at least one microtubule from each pole attaches to the kinetochore of each chromosome.

A tug-of-war then ensues as the chromosomes move back and forth toward the two poles. What Happens during Metaphase and Anaphase?