{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T11:48:31Z","timestamp":1777722511318,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,12,19]],"date-time":"2013-12-19T00:00:00Z","timestamp":1387411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:styled-content>Background<\/jats:styled-content>: The Matrigel\u2010embedded epithelium of the mouse submandibular gland undergoes branching morphogenesis when cultured in medium supplemented with fibroblast growth factor 7 (FGF7) and lysophosphatidic acid (LPA), whereas it elongates a stalk with limited branching in medium with only FGF7. Because LPA is a well\u2010known activator of epidermal growth factor (EGF) signaling, we hypothesized the involvement of autocrine EGF family growth factors in the branching morphogenesis. <jats:styled-content>Results:<\/jats:styled-content> Reverse transcriptase polymerase chain reaction studies showed that three members, <jats:italic>Tgfa<\/jats:italic>, <jats:italic>Hbegf<\/jats:italic>,and <jats:italic>Nrg1<\/jats:italic> of the EGF family were expressed in the epithelium cultured with FGF7\u2009+\u2009LPA as well as in the epithelium freshly isolated from the rudiments. All the growth factors induced extensive branching morphogenesis in the Matrigel\u2010embedded epithelium in the presence of LPA. Tyrphostin AG112, an inhibitor of EGF signaling, severely impaired branching morphogenesis induced by FGF7\u2009+\u2009LPA without exogenous addition of EGF family growth factors to the culture medium. The shaking cultures, which were expected to decrease the concentration of autocrine growth factors near the epithelium by promoting their diffusion, significantly reduced branching morphogenesis induced by FGF7\u2009+\u2009LPA. <jats:styled-content>Conclusions:<\/jats:styled-content> Autocrine EGF family growth factors are involved in epithelial branching morphogenesis induced by FGF7\u2009+\u2009LPA. <jats:italic>Developmental Dynamics 243:552\u2013559, 2014<\/jats:italic>. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.24097","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T02:17:02Z","timestamp":1384395422000},"page":"552-559","source":"Crossref","is-referenced-by-count":18,"title":["FGF7 signals are relayed to autocrine EGF family growth factors to induce branching morphogenesis of mouse salivary 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