Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The extracellular matrix guides the orientation of the cell division axis


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: The interphase cell shape is not the only parameter that determines the division axis.
Figure 2: Cell rounding and spindle orientation.
Figure 3: Distributions of actin-binding proteins and the role of actin and astral microtubules for spindle positioning on [L].
Figure 4: The absence of cortical heterogeneity leads to spindle mis-positioning.
Figure 5: The spatial distribution of ECM governs cortical heterogeneity and the orientation of the spindle.


  1. Palmer, R. E., Sullivan, D. S., Huffaker, T. & Koshland, D. Role of astral microtubules and actin in spindle orientation and migration in the budding yeast, Saccharomyces cerevisiae. J. Cell Biol. 119, 583–593 (1992).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  3. Tsou, M. F., Ku, W., Hayashi, A. & Rose, L. S. PAR-dependent and geometry-dependent mechanisms of spindle positioning. J. Cell Biol. 160, 845–855 (2003).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. O'Connell, C. B. & Wang, Y. L. Mammalian spindle orientation and position respond to changes in cell shape in a dynein-dependent fashion. Mol. Biol. Cell 11, 1765–1774 (2000).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Geiger, B., Bershadsky, A., Pankov, R. & Yamada, K. M. Transmembrane crosstalk between the extracellular matrix — cytoskeleton crosstalk. Nature Rev. Mol. Cell Biol. 2, 793–805 (2001).

    Article  CAS  Google Scholar 

  9. Whitesides, G. M., Ostuni, E., Takayama, S., Jiang, X. & Ingber, D. E. Soft lithography in biology and biochemistry. Annu. Rev. Biomed. Eng. 3, 335–373 (2001).

    Article  CAS  Google Scholar 

  10. Piel, M., Meyer, P., Khodjakov, A., Rieder, C. L. & Bornens, M. The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells. J. Cell Biol. 149, 317–330 (2000).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. Weed, S. A. & Parsons, J. T. Cortactin: coupling membrane dynamics to cortical actin assembly. Oncogene 20, 6418–6434 (2001).

    Article  CAS  Google Scholar 

  14. Louvet, S., Aghion, J., Santa-Maria, A., Mangeat, P. & Maro, B. Ezrin becomes restricted to outer cells following asymmetrical division in the preimplantation mouse embryo. Dev. Biol. 177, 568–579 (1996).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  16. Bretscher, A., Edwards, K. & Fehon, R. G. ERM proteins and merlin: integrators at the cell cortex. Nature Rev. Mol. Cell Biol. 3, 586–599 (2002).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  18. Angers-Loustau, A., Hering, R., Werbowetski, T. E., Kaplan, D. R. & Del Maestro, R. F. SRC regulates actin dynamics and invasion of malignant glial cells in three dimensions. Mol. Cancer Res. 2, 595–605 (2004).

    CAS  PubMed  Google Scholar 

  19. Hanke, J. H. 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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Tilghman, R. W. 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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  24. Busson, S., Dujardin, D., Moreau, A., Dompierre, J. & De Mey, J. R. Dynein and dynactin are localized to astral microtubules and at cortical sites in mitotic epithelial cells. Curr. Biol. 8, 541–544 (1998).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Wang, S. W., Griffin, F. J. & Clark, W. H., Jr. Cell-cell association directed mitotic spindle orientation in the early development of the marine shrimp Sicyonia ingentis. Development 124, 773–780 (1997).

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Book  Google Scholar 

  30. Cuvelier, D., Rossier, O., Bassereau, P. & Nassoy, P. 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).

    Article  CAS  Google Scholar 

Download references


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.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Michel Bornens.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Théry, M., Racine, V., Pépin, A. et al. The extracellular matrix guides the orientation of the cell division axis. Nat Cell Biol 7, 947–953 (2005).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing