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Experimental and theoretical study of mitotic spindle orientation

Nature volume 447, pages 493–496 (2007)Cite this article

Abstract

The architecture and adhesiveness of a cell microenvironment is a critical factor for the regulation of spindle orientation in vivo1,2. Using a combination of theory and experiments, we have investigated spindle orientation in HeLa (human) cells. Here we show that spindle orientation can be understood as the result of the action of cortical force generators, which interact with spindle microtubules and are activated by cortical cues. We develop a simple physical description of this spindle mechanics, which allows us to calculate angular profiles of the torque acting on the spindle, as well as the angular distribution of spindle orientations. Our model accounts for the preferred spindle orientation and the shape of the full angular distribution of spindle orientations observed in a large variety of different cellular microenvironment geometries. It also correctly describes asymmetric spindle orientations, which are observed for certain distributions of cortical cues. We conclude that, on the basis of a few simple assumptions, we can provide a quantitative description of the spindle orientation of adherent cells.

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Figure 1: Mitotic spindle orientation and cortical forces.
Figure 2: Spindle orientation on adhesive micropatterns, showing theoretical results and experimental data.
Figure 3: Spindle orientation changes induced by continuous displacements of cortical cues.
Figure 4: Transition from symmetric to asymmetric spindle orientation.

References

  1. Fuchs, E., Tumbar, T. & Guasch, G. Socializing with the neighbors: Stem cells and their niche. Cell 116, 769–778 (2004)

    Article  CAS  Google Scholar 

  2. Lu, B., Roegiers, F., Jan, L. Y. & Jan, Y. N. Adherens junctions inhibit asymmetric division in the Drosophila epithelium. Nature 409, 522–525 (2001)

    Article  ADS  CAS  Google Scholar 

  3. Grill, S. W., Howard, J., Schaffer, E., Stelzer, E. H. & Hyman, A. A. The distribution of active force generators controls mitotic spindle position. Science 301, 518–521 (2003)

    Article  ADS  CAS  Google Scholar 

  4. Colombo, K. et al. Translation of polarity cues into asymmetric spindle positioning in Caenorhabditis elegans embryos. Science 300, 1957–1961 (2003)

    Article  ADS  CAS  Google Scholar 

  5. Yamashita, Y. M., Jones, D. L. & Fuller, M. T. Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301, 1547–1550 (2003)

    Article  ADS  CAS  Google Scholar 

  6. Thery, M. & Bornens, M. Cell shape and cell division. Curr. Opin. Cell Biol. 18, 648–657 (2006)

    Article  CAS  Google Scholar 

  7. Lechler, T. & Fuchs, E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature 437, 275–280 (2005)

    Article  ADS  CAS  Google Scholar 

  8. Gong, Y., Mo, C. & Fraser, S. E. Planar cell polarity signalling controls cell division orientation during zebrafish gastrulation. Nature 430, 689–693 (2004)

    Article  ADS  CAS  Google Scholar 

  9. Siegrist, S. E. & Doe, C. Q. Extrinsic cues orient the cell division axis in Drosophila embryonic neuroblasts. Development 133, 529–536 (2006)

    Article  CAS  Google Scholar 

  10. Thery, M. et al. The extracellular matrix guides the orientation of the cell division axis. Nature Cell Biol. 7, 947–953 (2005)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Grill, S. W., Kruse, K. & Julicher, F. Theory of mitotic spindle oscillations. Phys. Rev. Lett. 94, 108104 (2005)

    Article  ADS  Google Scholar 

  13. Pecreaux, J. et al. Spindle oscillations during asymmetric cell division require a threshold number of active cortical force generators. Curr. Biol. 16, 2111–2122 (2006)

    Article  CAS  Google Scholar 

  14. Izumi, Y., Ohta, N., Hisata, K., Raabe, T. & Matsuzaki, F. Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization. Nature Cell Biol. 8, 586–593 (2006)

    Article  CAS  Google Scholar 

  15. Du, Q. & Macara, I. G. Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 119, 503–516 (2004)

    Article  CAS  Google Scholar 

  16. Sanada, K. & Tsai, L. H. G protein βγ subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors. Cell 122, 119–131 (2005)

    Article  CAS  Google Scholar 

  17. 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 

  18. 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 

Download references

Acknowledgements

Acknowledgments We thank A. Pépin and Y. Chen for technical help with micropattern fabrication, J.-B. Sibarita for technical help with video-microscopy, D. Grunwald for technical help with confocal image acquisitions and Y. Bellaïche for discussions.

Author Contributions M.T. performed experimental work, A.J.-D. performed numerical calculations, V.R. designed the software for movie analyses, and M.T., A.J.-D., M.B. and F.J. conceived the theoretical model.

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Author notes

  1. Manuel Théry and Andrea Jiménez-Dalmaroni: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut Curie, CNRS UMR144, Compartimentation et Dynamique Cellulaire, 26 rue d’Ulm, 75248 Paris, France,

    Manuel Théry, Victor Racine & Michel Bornens

  2. Commissariat à l’Energie Atomique, DSV, iRTSV, Laboratoire Biopuces, 17 rue des Martyrs, 38054 Grenoble, France,

    Manuel Théry

  3. Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Str. 38, 01187 Dresden, Germany,

    Andrea Jiménez-Dalmaroni & Frank Jülicher

Authors
  1. Manuel Théry
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  2. Andrea Jiménez-Dalmaroni
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  3. Victor Racine
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  4. Michel Bornens
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Correspondence to Michel Bornens or Frank Jülicher.

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Supplementary information

Supplementary Information

This file contains Supplementary Text with the full description of the model, Supplementary Discussion, Supplementary Figures S1- S3 with Legends and additional references. (PDF 1546 kb)

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Théry, M., Jiménez-Dalmaroni, A., Racine, V. et al. Experimental and theoretical study of mitotic spindle orientation. Nature 447, 493–496 (2007). https://doi.org/10.1038/nature05786

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