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The extracellular matrix guides the orientation of the cell division axis

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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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.

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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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Correspondence to Michel Bornens.

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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). https://doi.org/10.1038/ncb1307

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