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  • Review Article
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Mechanotransduction in development: a growing role for contractility

Nature Reviews Molecular Cell Biology volume 10, pages 34–43 (2009)Cite this article

Key Points

  • Traditionally, mechanotransduction research has studied the response of cells to applied forces. However, recent studies have shown that forces exerted through actomyosin-generated contractility can also trigger cellular signalling. Here, the role of such cell-generated forces is examined in the context of embryogenesis.

  • Embryogenesis can be described as the coordinated regulation of three basic cellular processes: proliferation, differentiation and spatial rearrangements of cells. There is evidence from both in vitro and in vivo systems that contractile forces regulate each of these cellular processes.

  • Mechanical cues regulate proliferation, at least in part, through regulation of RhoA-mediated cellular contractility. Both mathematical modelling of in vivo embryonic events and in vitro experimental evidence confirms that the mechanical stresses distributed throughout a tissue regulate localized proliferation; blocking contractility abrogates this growth regulation. In vitro work has further shown that both cytoskeletal tension and cell shape changes — both of which impinge on the RhoA–Rho kinase (ROCK) pathway — regulate proliferation.

  • Mechanotransduction and contractility regulate differentiation in vitro and in vivo. An interesting example is the stomodeal tissue compression that is caused by germband extension movements during Drosophila melanogaster gastrulation, which are proposed to activate Twist, an important regulator of differentiation of the digestive tract. Twist can then activate contractility downstream of Rho–ROCK activity to regulate apical constriction during mesoderm invagination.

  • The spatial organization of cells during development is highly regulated by cell-generated mechanical forces; this regulation is crucial for maintaining proper tissue structure and function. Examples of this regulation are tension-mediated serum response factor activity in D. melanogaster, Wnt activation of RhoA and contractility in Caenorhabditis elegans, Xenopus laevis and zebrafish, and contractility-driven zebrafish cell sorting and D. melanogaster intercalation.

  • Characterizing and manipulating forces in vivo is complicated. It will be important for the field to be able to draw from in vitro mechanotransduction studies to help interpret how cell-generated contractility and mechanical cues regulate developmental behaviours in vivo.

Abstract

Mechanotransduction research has focused historically on how externally applied forces can affect cell signalling and function. A growing body of evidence suggests that contractile forces that are generated internally by the actomyosin cytoskeleton are also important in regulating cell behaviour, and suggest a broader role for mechanotransduction in biology. Although the molecular basis for these cellular forces in mechanotransduction is being pursued in cell culture, researchers are also beginning to appreciate their contribution to in vivo developmental processes. Here, we examine the role for mechanical forces and contractility in regulating cell and tissue structure and function during development.

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Figure 1: Forces that regulate Drosophila melanogaster dorsal closure.
Figure 2: Cell shape regulates proliferation through the small GTPase RhoA.
Figure 3: Mechanical regulation of twist gene expression.
Figure 4: Forces regulate the spatial organization of cells.

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Acknowledgements

We apologize to authors whose papers could not be cited owing to space limitations. We thank R. Desai, J. Leight and L. Kwong for helpful comments. We acknowledge support from the National Institutes of Health (NIBIB, NHLBI and NIGMS) and the Army Research Office Multidisciplinary University Research Initiative. M.A.W. acknowledges financial support from the Ruth L. Kirschstein National Research Service Award.

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  1. Department of Bioengineering, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Michele A. Wozniak & Christopher S. Chen

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  1. Michele A. Wozniak
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Glossary

Morphogen

A diffusible signalling molecule that is usually found in a concentration gradient. Morphogens regulate tissue patterning during development.

Stiffness

The degree to which the surrounding adhesive scaffold resists deformation. Stiffness is also defined as the elastic modulus of a material.

Contractility

The ability of a cell to shorten or shrink in response to a stimulus. It is generated by the motor myosin II, which uses ATP hydrolysis to walk along actin filaments.

Convergence

Embryonic movements that mediolaterally narrow the tissue.

Mesoderm

One of the three germ layers that are produced by gastrulation. It gives rise to bone, muscle and connective tissue.

Notochord

A flexible rod of mesodermal cells that defines the axis of the embryo to provide support.

Involuting marginal zone

The vegetal portion of the marginal zone (a region between the animal and vegetal hemispheres) of the X. laevis embryo that turns inside the embryo during involution.

Mesenchymal stem cell

A multipotent stem cell that retains the ability to differentiate into multiple cell types.

Dorsal closure

The process during D. melanogaster embryogenesis whereby the two sides of epidermal tissue grow to close and cover the dorsal opening. During this time, the underlying amnioserosa is also stretched to separate the yolk sac from the vitelline envelope.

Egg chamber

A chamber in D. melanogaster that consists of a germline cyst that is covered by a somatic epithelium. During morphogenesis, the cyst grows in a proliferation-independent manner, whereas the epithelium grows by proliferation.

Blastocyst

A structure in early embryogenesis that contains the inner cell mass. The blastocyst gives rise to the embryo.

Poly(2-hydroxyethyl methacrylate)

(polyHEMA). A hydrophilic polymer that prevents cell attachment and spreading.

Microcontact printing

A method in which an elastomeric stamp with relief features is used to transfer 'inked' molecules (usually self-assembled monolayers or ECM proteins) onto the surface of a substrate through conformal contact.

Germband extension

The process by which the D. melanogaster embryo lengthens and narrows during gastrulation.

Apical constriction

Apically localized actomyosin-driven inward bending of tissue to promote invagination.

Formin

A protein that nucleates actin filaments to promote elongation.

Intercalation

The process by which cells rearrange and exchange neighbours to result in one plane of cells. This thins and expands the tissue during epiboly and convergence or extension.

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Wozniak, M., Chen, C. Mechanotransduction in development: a growing role for contractility. Nat Rev Mol Cell Biol 10, 34–43 (2009). https://doi.org/10.1038/nrm2592

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