Letter | Published:

A tension-induced mechanotransduction pathway promotes epithelial morphogenesis

Nature volume 471, pages 99103 (03 March 2011) | Download Citation

Abstract

Mechanotransduction refers to the transformation of physical forces into chemical signals. It generally involves stretch-sensitive channels or conformational change of cytoskeleton-associated proteins1. Mechanotransduction is crucial for the physiology of several organs and for cell migration2,3. The extent to which mechanical inputs contribute to development, and how they do this, remains poorly defined. Here we show that a mechanotransduction pathway operates between the body-wall muscles of Caenorhabditis elegans and the epidermis. This pathway involves, in addition to a Rac GTPase, three signalling proteins found at the hemidesmosome: p21-activated kinase (PAK-1), the adaptor GIT-1 and its partner PIX-1. The phosphorylation of intermediate filaments is one output of this pathway. Tension exerted by adjacent muscles or externally exerted mechanical pressure maintains GIT-1 at hemidesmosomes and stimulates PAK-1 activity through PIX-1 and Rac. This pathway promotes the maturation of a hemidesmosome into a junction that can resist mechanical stress and contributes to coordinating the morphogenesis of epidermal and muscle tissues. Our findings suggest that the C. elegans hemidesmosome is not only an attachment structure, but also a mechanosensor that responds to tension by triggering signalling processes. We suggest that similar pathways could promote epithelial morphogenesis or wound healing in other organisms in which epithelial cells adhere to tension-generating contractile cells.

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Acknowledgements

We are grateful to H.-J. Cheng, the CGC and NBP-Japan, L. Lim, J. Nance, C. Gally and L. Broday for reagents, as well as M. Argentini for technical advice. We thank J. Ahringer for a discussion, and O. Pourquié, J.-L. Bessereau, S. Jarriault and members of the Labouesse laboratory (C. Gally, I. Kolotueva, N. Osmani and S. Quintin) for critical reading of the manuscript. This work was supported by grants from the ANR, ARC and EU (STREP-FP6 programme) (M.L.) and by institutional funds from the CNRS and INSERM.

Author information

Author notes

    • Frédéric Landmann

    Present address: MCBD Department, University of California, Santa Cruz, California 95064, USA .

    • Frédéric Landmann
    •  & Hala Zahreddine

    These authors contributed equally to this work.

Affiliations

  1. Development and Stem Cells Program, IGBMC, CNRS (UMR7104), INSERM (U964), Université de Strasbourg, 1 rue Laurent Fries, BP10142, 67400 Illkirch, France

    • Huimin Zhang
    • , Frédéric Landmann
    • , Hala Zahreddine
    • , David Rodriguez
    •  & Michel Labouesse
  2. Imaging Centre, IGBMC, CNRS (UMR7104), INSERM (U964), Université de Strasbourg, 1 rue Laurent Fries, BP10142, 67400 Illkirch, France

    • Marc Koch

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Contributions

H. Zhang and M.L. designed the study, analysed the data and wrote the paper. H. Zhang conducted most of the experiments. F.L. and H. Zahreddine made some initial observations (tension-change modification of the epidermis, and PAK-1 distribution and mutant phenotype) that proved to be essential for designing the study. D.R. provided technical help. M.K. helped to design and analyse the pressing experiment.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Michel Labouesse.

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DOI

https://doi.org/10.1038/nature09765

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