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.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Rappaport, R. Cytokinesis in Animal Cells (Cambridge Univ, Cambridge, UK, 1997)
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)
White, J. G. & Borisy, G. G. On the mechanism of cytokinesis in animal cells. J. Theor. Biol. 101, 289–316 (1983)
Mandato, C. A., Benink, H. A. & Bement, W. M. Microtubule–actomyosin interactions in cortical flow and cytokinesis. Cell Motil. Cytoskeleton 45, 87–92 (2000)
Wolf, N., Hirsh, D. & McIntosh, J. R. Spermatogenesis in males of the free-living nematode, Caenorhabditis elegans. J. Ultrastruct. Res. 63, 155–169 (1978)
Rappaport, R. Experiments concerning the cleavage stimulus in sand dollar eggs. J. Exp. Zool. 148, 81–89 (1961)
Mayer, T. U. et al. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 286, 971–974 (1999)
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)
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)
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)
Canman, J. C., Salmon, E. D. & Fang, G. Inducing precocious anaphase in cultured mammalian cells. Cell Motil. Cytoskeleton 52, 61–65 (2002)
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)
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)
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)
Adams, R. R., Carmena, M. & Earnshaw, W. C. Chromosomal passengers and the (aurora) ABCs of mitosis. Trends Cell Biol. 11, 49–54 (2001)
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)
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)
Kurz, T. et al. Cytoskeletal regulation by the Nedd8 ubiquitin-like protein modification pathway. Science 295, 1294–1298 (2002)
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)
Asnes, C. F. & Schroeder, T. E. Cell cleavage. Ultrastructural evidence against equatorial stimulation by aster microtubules. Exp. Cell Res. 122, 327–338 (1979)
Wittmann, T. & Waterman-Storer, C. M. Cell motility: can Rho GTPases and microtubules point the way? J. Cell Sci. 114, 3795–3803 (2001)
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)
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)
Radley, J. M. & Scurfield, G. The mechanism of platelet release. Blood 56, 996–999 (1980)
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)
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.
The authors declare that they have no competing financial interests.
About this article
Cite this article
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
Nature Communications (2021)
Current Genetics (2020)
Mitsui-7, heat-treated, and nitrogen-doped multi-walled carbon nanotubes elicit genotoxicity in human lung epithelial cells
Particle and Fibre Toxicology (2019)
Nature Communications (2017)
Nature Reviews Molecular Cell Biology (2016)