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      Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria

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          Abstract

          The modulation of developmental biochemical pathways by mechanical cues is an emerging feature of animal development, but its evolutionary origins have not been explored. Here we show that a common mechanosensitive pathway involving β-catenin specifies early mesodermal identity at gastrulation in zebrafish and Drosophila. Mechanical strains developed by zebrafish epiboly and Drosophila mesoderm invagination trigger the phosphorylation of β-catenin–tyrosine-667. This leads to the release of β-catenin into the cytoplasm and nucleus, where it triggers and maintains, respectively, the expression of zebrafish brachyury orthologue notail and of Drosophila Twist, both crucial transcription factors for early mesoderm identity. The role of the β-catenin mechanosensitive pathway in mesoderm identity has been conserved over the large evolutionary distance separating zebrafish and Drosophila. This suggests mesoderm mechanical induction dating back to at least the last bilaterian common ancestor more than 570 million years ago, the period during which mesoderm is thought to have emerged.

          Abstract

          Mechanical cues can induce morphogenetic processes during development. Here the authors show that mechanical changes during embryonic development in both zebrafish and Drosophila lead to nuclear localization of β-catenin, which regulates genes required for early mesoderm development in both species.

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          Most cited references53

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          Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF.

          The vertebrate transcription factors TCF (T cell factor) and LEF (lymphocyte enhancer binding factor) interact with beta-catenin and are hypothesized to mediate Wingless/Wnt signaling. We have cloned a maternally expressed Drosophila TCF family member, dTCF. dTCF binds a canonical TCF DNA motif and interacts with the beta-catenin homolog Armadillo. Previous studies have identified two regions in Armadillo required for Wingless signaling. One of these interacts with dTCF, while the other constitutes a transactivation domain. Mutations in dTCF and expression of a dominant-negative dTCF transgene cause a segment polarity phenotype and affect expression of the Wingless target genes engrailed and Ultrabithorax. Epistasis analysis positions dTCF downstream of armadillo. The Armadillo-dTCF complex mediates Wingless signaling as a bipartite transcription factor.
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            Mechanotransduction in development: a growing role for contractility.

            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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              Actomyosin-Mediated Cellular Tension Drives Increased Tissue Stiffness and β-Catenin Activation to Induce Epidermal Hyperplasia and Tumor Growth

              Tumors and associated stroma manifest mechanical properties that promote cancer. Mechanosensation of tissue stiffness activates the Rho/ROCK pathway to increase actomyosin-mediated cellular tension to re-establish force equilibrium. To determine how actomyosin tension affects tissue homeostasis and tumor development, we expressed conditionally active ROCK2 in mouse skin. ROCK activation elevated tissue stiffness via increased collagen. β-catenin, a key element of mechanotranscription pathways, was stabilized by ROCK activation leading to nuclear accumulation, transcriptional activation, and consequent hyperproliferation and skin thickening. Inhibiting actomyosin contractility by blocking LIMK or myosin ATPase attenuated these responses, as did FAK inhibition. Tumor number, growth, and progression were increased by ROCK activation, while ROCK blockade was inhibitory, implicating actomyosin-mediated cellular tension and consequent collagen deposition as significant tumor promoters. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Pub. Group
                2041-1723
                27 November 2013
                : 4
                : 2821
                Affiliations
                [1 ]Mechanics and Genetics of Embryonic Development Group, PSL Research University, CNRS, UMR168, Inserm, Institut Curie , 11 rue Pierre et Marie Curie, 75005 Paris, France
                [2 ]Physico-Chemistry of Electrolytes and Colloïds, CNRS UMR 7195—UPMC—ESPCI , 2 place Jussieu, 75005 Paris, France
                [3 ]Univ. Grenoble Alpes, Inst NEEL , F-38042 Grenoble, France
                [4 ]CNRS, Inst NEEL , F-38042 Grenoble, France
                [5 ]Zebrafish Models of Neurodegenerative Disorders, Inserm, Hôpital Robert Debré , U676 Paris, France
                [6 ]Institut Jacques Monod, CNRS, UMR 7592, Univ Paris Diderot, Sorbonne Paris Cité , F-75205 Paris, France
                [7 ]These authors contributed equally to the work
                [8 ]Present address: Developmental Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany
                Author notes
                Article
                ncomms3821
                10.1038/ncomms3821
                3868206
                24281726
                96407637-39ef-4368-af31-a51bd563231d
                Copyright © 2013, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

                This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this licence visit http://creativecommons.org/licenses/by/3.0/.

                History
                : 21 June 2013
                : 24 October 2013
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