Chromosome spindle

The centrioles migrate to opposite poles of the cell and the mitotic spindle is formed, apparently joining the cell membrane through the centrioles to the centromere of each chromosome. Spindle fibres consist of one type of protein, tubulin, of molecular weight 60,000. It is the organisation of these molecules to form the mitotic spindle which is blocked by the drugs colchicine, colcemide, nocodazole, vincristine and vinblastine (Fig. 10.3) with the consequence that mitosis is arrested in metaphase. 

Lampson MA, Renduchitala K, Khodjakov A, Kapoor TM. Cor- 58. reeling improper chromosome-spindle attachments during cell division. Nat. Cell Biol. 2004 6 232-237. 

Correcting improper chromosome-spindle attachments during cell division, Nat. Cell Biol. 

Fig. 1. A living primary spermatocyte of Pardalophora apiculata (a grasshopper) as viewed in Inoue s rectified polarizing microscope. A., Metaphase kinetochores of one bivalent are indicated by arrows ("k ) and polar regions by p". Birefringent chromosomal spindle fibers run from each kinetochore toward a pole the diffuse background birefringence of interpolar fibers is identified only with difficulty In the prints but Is readily measured. B., Metaphase the opposite compensator setting. C, D. Anaphase 22 and 36 minutes, respectively, after A. XI,500.

ANAPHASE. The two forms of anaphase motion can be directly related to the spindle mechanics reviewed above as follows (Ris, 1949) The movement to the poles depends upon force production or at least transmission by shortening chromosomal spindle fibers. Spindle elongation results from lenghtening of the interpolar fibers, which produces increased chromosome separation because the chromosomal fibers are anchored to the interpolar fibers. There is at present no reason to doubt the correctness of this consistent and straightforward view (reviewed by Ris, 1955 Mazia, 1961). 

Chromosomes are individually attached to the spindle by chromosomal spindle fibers rigid enough to bear any normal mitotic force. The separation of the poles is... 

Prometaphase congression is caused chiefly by poleward forces, but lengthening of chromosomal fibers may play some role in most cells. In a restricted class of spindles, motion of individual chromosome spindle units relative to others may produce congression.) This would account for the motion itself, but why it leads to a position midway between the poles is not understood. 

Hypotheses of Force Production. This discussion will center on the molecular mechanisms by which poleward forces might be produced. Given the mechanical and physiological attributes of the area between the kinetochores and the poles, and the presence there of chromosomal spindle fibers, it is hardly surprising that current speculations revive an old idea—the traction fiber. These speculations are briefly reviewed here. For critiques of the ingenious alternatives advanced earlier, see Schrader, 1953 Mazia, 1961 and Taylor, 1965a. 

Three fundamental principles have been known for some time and these underlie all further analysis 1. The distribution of chromosomes is determined by kinetochore orientation—the association of a kinetochore with a particular pole by chromosomal spindle fibers. Thus the chromosome moves in anaphase to that pole, and the usual equipartition of chromosomes occurs because the partner half-bivalents comprising each bivalent are oriented to opposite poles—orientation (see Fig. 11). 2. Kinetochore orientation is established during prometaphase. Already suggested by studies of fixed material, this was conclusively documented in living cells by Dietz (1956). 3. The initial orientation established at the start of prometaphase is often inappropriate. For example, in crane fly meiosis, 10 percent of the bivalents initially shows unipolar orientation (Bauer et al., 1961), i.e., both half-bivalents are oriented to the same pole (see Fig. 11). Nondisjunction and abnormal chromosome complements would inevitably ensue if such... 

Fig. 11. Semidiagrammatic representation of orientation at meiotic prometaphase I. Four bivalents, each composed of two chromosomes (half-bivalents) are shown with their chromosomal spindle fibers (broken lines). Three bivalents (above) are shown in bipolar orientation in each, the partner half-bivalents are oriented to opposite poles. One bivalent (below) is shown In unipolar malorientation. Both half-bivalents are oriented to the lower pole (the arrow Indicates the direction of artificial force applied in tension experiments described below. (From Nicklas and Koch. 1969. J. Cell Biol., 43 40-50.)...

The fine structural and molecular events during reorientation are similarly unknown. Reorientation surely involves the loss and reformation of chromosomal spindle fibers (p. 261). But even whether loss and reformation are sequential or concurrent at one kinetochore is uncertain (brief review and speculation, Nicklas and Koch, 1969). Again, correlated in-vivo and electron microscopic observations on the same chromosome will be required. 

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