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The extracellular matrix guides the orientation of the cell division axis

Nature Cell Biology volume 7, pages 947953 (2005) | Download Citation

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Abstract

The cell division axis determines the future positions of daughter cells and is therefore critical for cell fate. The positioning of the division axis has been mostly studied in systems such as embryos or yeasts, in which cell shape is well defined1,2. In these cases, cell shape anisotropy and cell polarity affect spindle orientation3,4,5. It remains unclear whether cell geometry or cortical cues are determinants for spindle orientation in mammalian cultured cells6,7. The cell environment is composed of an extracellular matrix (ECM), which is connected to the intracellular actin cytoskeleton via transmembrane proteins8. We used micro-contact printing to control the spatial distribution of the ECM on the substrate9 and demonstrated that it has a role in determining the orientation of the division axis of HeLa cells. On the basis of our analysis of the average distributions of actin-binding proteins in interphase and mitosis, we propose that the ECM controls the location of actin dynamics at the membrane, and thus the segregation of cortical components in interphase. This segregation is further maintained on the cortex of mitotic cells and used for spindle orientation.

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References

  1. 1.

    , , & Role of astral microtubules and actin in spindle orientation and migration in the budding yeast, Saccharomyces cerevisiae. J. Cell Biol. 119, 583–593 (1992).

  2. 2.

    Mechanisms of spindle positioning: focus on flies and worms. Trends Cell Biol. 12, 332–339 (2002).

  3. 3.

    , , & PAR-dependent and geometry-dependent mechanisms of spindle positioning. J. Cell Biol. 160, 845–855 (2003).

  4. 4.

    et al. First cleavage of the mouse embryo responds to change in egg shape at fertilization. Curr. Biol. 14, 397–405 (2004).

  5. 5.

    Control of cell polarity and mitotic spindle positioning in animal cells. Curr. Opin. Cell Biol. 15, 73–81 (2003).

  6. 6.

    & Mammalian spindle orientation and position respond to changes in cell shape in a dynein-dependent fashion. Mol. Biol. Cell 11, 1765–1774 (2000).

  7. 7.

    & Orientation of spindle axis and distribution of plasma membrane proteins during cell division in polarized MDCKII cells. J. Cell Biol. 126, 1509–1526 (1994).

  8. 8.

    , , & Transmembrane crosstalk between the extracellular matrix — cytoskeleton crosstalk. Nature Rev. Mol. Cell Biol. 2, 793–805 (2001).

  9. 9.

    , , , & Soft lithography in biology and biochemistry. Annu. Rev. Biomed. Eng. 3, 335–373 (2001).

  10. 10.

    , , , & The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells. J. Cell Biol. 149, 317–330 (2000).

  11. 11.

    & Determination of cell division axes in the early embryogenesis of Caenorhabditis elegans. J. Cell Biol. 105, 2123–2135 (1987).

  12. 12.

    et al. Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces. FASEB J. 16, 1195–1204 (2002).

  13. 13.

    & Cortactin: coupling membrane dynamics to cortical actin assembly. Oncogene 20, 6418–6434 (2001).

  14. 14.

    , , , & Ezrin becomes restricted to outer cells following asymmetrical division in the preimplantation mouse embryo. Dev. Biol. 177, 568–579 (1996).

  15. 15.

    et al. Phosphoinositide binding and phosphorylation act sequentially in the activation mechanism of ezrin. J. Cell Biol. 164, 653–659 (2004).

  16. 16.

    , & ERM proteins and merlin: integrators at the cell cortex. Nature Rev. Mol. Cell Biol. 3, 586–599 (2002).

  17. 17.

    Actin based motility on retraction fibers in mitotic PtK2 cells. Cell Motil. Cytoskeleton 22, 135–151 (1992).

  18. 18.

    , , , & SRC regulates actin dynamics and invasion of malignant glial cells in three dimensions. Mol. Cancer Res. 2, 595–605 (2004).

  19. 19.

    et al. Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation. J. Biol. Chem. 271, 695–701 (1996).

  20. 20.

    et al. SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling. Mol. Cell. Biol 20, 9018–9027 (2000).

  21. 21.

    , & Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. J. Cell Biol. 159, 881–891 (2002).

  22. 22.

    et al. Focal adhesion kinase is required for the spatial organization of the leading edge in migrating cells. J. Cell Sci. 118, 2613–2623 (2005).

  23. 23.

    & Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity. Nature 421, 753–756 (2003).

  24. 24.

    , , , & Dynein and dynactin are localized to astral microtubules and at cortical sites in mitotic epithelial cells. Curr. Biol. 8, 541–544 (1998).

  25. 25.

    et al. A role for cytoplasmic dynein and LIS1 in directed cell movement. J. Cell Biol. 163, 1205–1211 (2003).

  26. 26.

    et al. A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function. Nature Cell Biol. 2, 784–791 (2000).

  27. 27.

    , & Cell-cell association directed mitotic spindle orientation in the early development of the marine shrimp Sicyonia ingentis. Development 124, 773–780 (1997).

  28. 28.

    Cell contacts orient some cell division axes in the Caenorhabditis elegans embryo. J. Cell Biol. 129, 1071–1080 (1995).

  29. 29.

    & in Alternative Lithography (ed. Sotomayor Torres, C. M.) 305–330 (Kluwer Academic/Plenum, Boston/Dordrecht/London, 2003).

  30. 30.

    , , & Micropatterned “adherent/repellent” glass surfaces for studying the spreading kinetics of individual red blood cells onto protein-decorated substrates. Eur. Biophys. J. 32, 342–354 (2003).

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Acknowledgements

We would like to thank Y. Bellaiche and P. Chavrier for helpful discussions, D. E. Ingber for technical help during preliminary experiments, and M. Morgan and J. Sillibourne for carefully reading this manuscript. Part of this work was carried out in the clean room facility of the UMR168 at the Institut Curie. Supported by CNRS, Institut Curie and by HSFP, grant Ref RGP0064/2004 to M.B.

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  1. Biologie du cycle cellulaire et de la motilité, UMR144, CNRS, Institut Curie, 26 rue d'Ulm 75248 Paris Cedex 05, France.

    • Manuel Théry
    • , Matthieu Piel
    •  & Michel Bornens
  2. Centre d'imagerie, UMR144, CNRS, Institut Curie, 26 rue d'Ulm 75248 Paris Cedex 05, France.

    • Victor Racine
    •  & Jean-Baptiste Sibarita
  3. Groupe nanotechnologie et dispositifs microfluidiques, UPR20, CNRS, Laboratoire Photonique et Nanostructures, Route de Nozay, 91460 Marcoussis, France.

    • Anne Pépin
    •  & Yong Chen

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The authors declare no competing financial interests.

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Correspondence to Michel Bornens.

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https://doi.org/10.1038/ncb1307

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