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Determining the position of the cell division plane

Abstract

Proper positioning of the cell division plane during mitosis is essential for determining the size and position of the two daughter cells—a critical step during development and cell differentiation1. A bipolar microtubule array has been proposed to be a minimum requirement for furrow positioning in mammalian cells, with furrows forming at the site of microtubule plus-end overlap between the spindle poles2,4,4. Observations in other species have suggested, however, that this may not be true5,6. Here we show, by inducing mammalian tissue cells with monopolar spindles to enter anaphase7,8, that furrow formation in cultured mammalian cells does not require a bipolar spindle. Unexpectedly, cytokinesis occurs at high frequency in monopolar cells. Division always occurs at a cortical position distal to the chromosomes. Analysis of microtubules during cytokinesis in cells with monopolar and bipolar spindles shows that a subpopulation of stable microtubules extends past chromosomes and binds to the cell cortex at the site of furrow formation. Our data are consistent with a model in which chromosomes supply microtubules with factors that promote microtubule stability and furrowing.

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Figure 1: Cytokinesis in cells with monopolar spindles a, Monastrol-treated PtK1 cell in prometaphase cell stained for tubulin (green) and DNA (red).
Figure 2: INCENP localizes to furrows in cells with monopolar spindles.
Figure 3: Chromosome-associated stable microtubules at the furrow.
Figure 4: Model of cytokinesis induced by monopolar spindles.

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References

  1. Rappaport, R. Cytokinesis in Animal Cells (Cambridge Univ, Cambridge, UK, 1997)

    Google Scholar 

  2. Harris, A. K. & Gewalt, S. L. Simulation testing of mechanisms for inducing the formation of the contractile ring in cytokinesis. J. Cell Biol. 109, 2215–2223 (1989)

    Article  CAS  Google Scholar 

  3. White, J. G. & Borisy, G. G. On the mechanism of cytokinesis in animal cells. J. Theor. Biol. 101, 289–316 (1983)

    Article  CAS  Google Scholar 

  4. Mandato, C. A., Benink, H. A. & Bement, W. M. Microtubule–actomyosin interactions in cortical flow and cytokinesis. Cell Motil. Cytoskeleton 45, 87–92 (2000)

    Article  CAS  Google Scholar 

  5. Wolf, N., Hirsh, D. & McIntosh, J. R. Spermatogenesis in males of the free-living nematode, Caenorhabditis elegans. J. Ultrastruct. Res. 63, 155–169 (1978)

    Article  CAS  Google Scholar 

  6. Rappaport, R. Experiments concerning the cleavage stimulus in sand dollar eggs. J. Exp. Zool. 148, 81–89 (1961)

    Article  CAS  Google Scholar 

  7. Mayer, T. U. et al. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 286, 971–974 (1999)

    Article  CAS  Google Scholar 

  8. Kapoor, T. M., Mayer, T. U., Coughlin, M. L. & Mitchison, T. J. Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J. Cell Biol. 150, 975–988 (2000)

    Article  CAS  Google Scholar 

  9. Canman, J. C., Hoffman, D. B. & Salmon, E. D. The role of pre- and post-anaphase microtubules in the cytokinesis phase of the cell cycle. Curr. Biol. 10, 611–614 (2000)

    Article  CAS  Google Scholar 

  10. Gorbsky, G. J., Chen, R. H. & Murray, A. W. Microinjection of antibody to Mad2 protein into mammalian cells in mitosis induces premature anaphase. J. Cell Biol. 141, 1193–1205 (1998)

    Article  CAS  Google Scholar 

  11. Canman, J. C., Salmon, E. D. & Fang, G. Inducing precocious anaphase in cultured mammalian cells. Cell Motil. Cytoskeleton 52, 61–65 (2002)

    Article  Google Scholar 

  12. Canman, J. C. et al. Anaphase onset does not require the microtubule-dependent depletion of kinetochore and centromere-binding proteins. J. Cell Sci. 115, 3787–3795 (2002)

    Article  CAS  Google Scholar 

  13. Wheatley, S. P., Kandels-Lewis, S. E., Adams, R. R., Ainsztein, A. M. & Earnshaw, W. C. INCENP binds directly to tubulin and requires dynamic microtubules to target to the cleavage furrow. Exp. Cell Res. 262, 122–127 (2001)

    Article  CAS  Google Scholar 

  14. Murata-Hori, M. & Wang, Y. L. Both midzone and astral microtubules are involved in the delivery of cytokinesis signals: insights from the mobility of aurora B. J. Cell Biol. 159, 45–53 (2002)

    Article  CAS  Google Scholar 

  15. Adams, R. R., Carmena, M. & Earnshaw, W. C. Chromosomal passengers and the (aurora) ABCs of mitosis. Trends Cell Biol. 11, 49–54 (2001)

    Article  CAS  Google Scholar 

  16. Mackay, A. M., Ainsztein, A. M., Eckley, D. M. & Earnshaw, W. C. A dominant mutant of inner centromere protein (INCENP), a chromosomal protein, disrupts prometaphase congression and cytokinesis. J. Cell Biol. 140, 991–1002 (1998)

    Article  CAS  Google Scholar 

  17. Shannon, K. B., Canman, J. C. & Salmon, E. D. Mad2 and BubR1 function in a single checkpoint pathway that responds to a loss of tension. Mol. Biol. Cell 13, 3706–3719 (2002)

    Article  CAS  Google Scholar 

  18. Kurz, T. et al. Cytoskeletal regulation by the Nedd8 ubiquitin-like protein modification pathway. Science 295, 1294–1298 (2002)

    Article  ADS  CAS  Google Scholar 

  19. Dechant, R. & Glotzer, M. Centrosome separation and central spindle assembly act in redundant pathways that regulate microtubule density and trigger cleavage furrow formation. Dev. Cell 4, 333–344 (2003)

    Article  CAS  Google Scholar 

  20. Asnes, C. F. & Schroeder, T. E. Cell cleavage. Ultrastructural evidence against equatorial stimulation by aster microtubules. Exp. Cell Res. 122, 327–338 (1979)

    Article  CAS  Google Scholar 

  21. Wittmann, T. & Waterman-Storer, C. M. Cell motility: can Rho GTPases and microtubules point the way? J. Cell Sci. 114, 3795–3803 (2001)

    CAS  PubMed  Google Scholar 

  22. Kubai, D. F. Meiosis in Sciara coprophila: structure of the spindle and chromosome behavior during the first meiotic division. J. Cell Biol. 93, 655–669 (1982)

    Article  CAS  Google Scholar 

  23. Foe, V. E., Field, C. M. & Odell, G. M. Microtubules and mitotic cycle phase modulate spatiotemporal distributions of F-actin and myosin II in Drosophila syncytial blastoderm embryos. Development 127, 1767–1787 (2000)

    CAS  PubMed  Google Scholar 

  24. Radley, J. M. & Scurfield, G. The mechanism of platelet release. Blood 56, 996–999 (1980)

    CAS  PubMed  Google Scholar 

  25. Howell, B. J., Hoffman, D. B., Fang, G., Murray, A. W. & Salmon, E. D. Visualization of Mad2 dynamics at kinetochores, along spindle fibres, and at spindle poles in living cells. J. Cell Biol. 150, 1233–1250 (2000)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank B. Bowerman, J. Sekelsky, N. Salmon, A. Harris and K. Bloom for comments on the manuscript; C. Waterman-Storer for discussions; the Cell Division Group at the Marine Biological Laboratory in Woods Hole; and B. Howell, D. Cimini, J. DeLuca, K. Shannon, C. Pearson, B. Moree and all members of the Salmon laboratory for support.

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Correspondence to E. D. Salmon.

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Canman, J., Cameron, L., Maddox, P. et al. Determining the position of the cell division plane. Nature 424, 1074–1078 (2003). https://doi.org/10.1038/nature01860

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