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In the pharyngeal region of the vertebrate embryo, endodermal epithelium is reiteratively folded outward to form pharyngeal pouches, making partitions between the pharyngeal arches. <jats:italic>Ripply3<\/jats:italic>, encoding a member of the Ripply family of adaptor proteins, is required for the pouch formation posterior to the 2nd pharyngeal pouch. In this study, we found that the expression of mouse <jats:italic>Ripply3<\/jats:italic> was specifically activated in accordance with the bending of the endodermal epithelium during the pouch formation. In <jats:italic>Ripply3\u2010<\/jats:italic>deficient embryos, a continuous monolayer of the endodermal epithelium was not maintained posterior to the 2nd pharyngeal pouch. Corresponding to the endodermal region of the deformed epithelium, the activated form of Integrin \u03b21, which was localized at the basal side of the epithelial cells in the wild\u2010type embryos, was not persistently observed in the mutants. On the other hand, cell proliferation and apoptotic cell death in the endoderm were not obviously affected by the <jats:italic>Ripply3<\/jats:italic> deficiency. Significantly, Ripply3 expressed in cultured cells was found to be preferentially accumulated in the focal adhesions, which are Integrin\u2010mediated adhesive contact sites transmitting mechanical force between the extracellular matrix and attached cells. Furthermore, Ripply3 promoted the maturation of focal adhesions in these cells. Thus, Ripply3 appears to have been activated to enhance the connection between the extracellular matrix and endodermal epithelial cells, as a mechanism to resist the mechanical stress generated during the bending of the epithelial sheets.<\/jats:p>","DOI":"10.1111\/dgd.12425","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T06:15:57Z","timestamp":1519366557000},"page":"87-96","source":"Crossref","is-referenced-by-count":5,"title":["<i>Ripply3<\/i> is required for the maintenance of epithelial sheets in the morphogenesis of pharyngeal pouches"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8643-2493","authenticated-orcid":false,"given":"Yoshihiro","family":"Tsuchiya","sequence":"first","affiliation":[{"name":"Okazaki Institute for Integrative Bioscience and National Institute for Basic Biology National Institutes of Natural Sciences  Okazaki Japan"},{"name":"Department of Basic Biology SOKENDAI (Graduate School 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