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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,5,16]]},"abstract":"<jats:p>\n                    Implantation is the first direct encounter between the embryo and uterus during pregnancy, and\n                    <jats:italic>Hbegf<\/jats:italic>\n                    is the earliest known molecular signaling for embryo\u2013uterine crosstalk during implantation. The downstream effectors of heparin-binding EGF (HB-EGF) in implantation remain elusive due to the complexity of EGF receptor family. This study shows that the formation of implantation chamber (crypt) triggered by HB-EGF is disrupted by uterine deletion of\n                    <jats:italic>Vangl2,<\/jats:italic>\n                    a key planar cell polarity component (PCP). We found that HB-EGF binds to ERBB2 and ERBB3 to recruit VANGL2 for tyrosine phosphorylation. Using in vivo models, we show that uterine VAGL2 tyrosine phosphorylation is suppressed in\n                    <jats:italic>Erbb2\/Erbb3<\/jats:italic>\n                    double conditional knockout mice. In this context, severe implantation defects in these mice lend support to the critical role of HB-EGF-ERBB2\/3-VANGL2 in establishing a two-way dialogue between the blastocyst and uterus. In addition, the result addresses an outstanding question how VANGL2 is activated during implantation. Taken together, these observations reveal that HB-EGF regulates the implantation process by influencing uterine epithelial cell polarity comprising VANGL2.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2302937120","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T15:17:50Z","timestamp":1683559070000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["An unanticipated discourse of HB-EGF with VANGL2 signaling during embryo implantation"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4854-8334","authenticated-orcid":false,"given":"Yeon Sun","family":"Kim","sequence":"first","affiliation":[{"name":"Center of Reproductive Sciences, Division of Developmental Biology, Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 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