Details

Autor(en) / Beteiligte

• Chen, Christopher S
• Wozniak, Michele A

Titel

Mechanotransduction in development: a growing role for contractility

Ist Teil von

• Nature reviews. Molecular cell biology, 2009-01, Vol.10 (1), p.34-43

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 . Mechanical forces regulate basic cellular processes, such as proliferation, differentiation and tissue organization during embryogenesis. What are the mechanisms that underlie force-induced mechanotransduction during development? And what is the role of actomyosin-mediated contractile forces in the regulation of cell and tissue structure and function? 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.