{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T01:06:34Z","timestamp":1782781594814,"version":"3.54.5"},"reference-count":50,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DE026537"],"award-info":[{"award-number":["DE026537"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006156","name":"Sidney Kimmel Foundation for Cancer Research","doi-asserted-by":"publisher","award":["SKF-15-165"],"award-info":[{"award-number":["SKF-15-165"]}],"id":[{"id":"10.13039\/100006156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Cleft palate (CP), one of the most common congenital diseases, arises from failures in secondary palatogenesis during embryonic development. Several human genetic syndromes featuring CP and ectodermal dysplasia have been linked to mutations in genes regulating cell-cell adhesion, yet mouse models have largely failed to recapitulate these findings. Here, we utilize in utero lentiviral-mediated genetic approaches in mice to provide the first direct evidence that the nectin-afadin axis is essential for proper palate shelf elevation and fusion. Using this technique, we demonstrate that palatal epithelial conditional loss of afadin (Afdn)\u2014an obligate nectin- and actin-binding protein\u2014induces a high penetrance of CP, not observed when Afdn is targeted later using Krt14-Cre. We implicate Nectin1 and Nectin4 as critical players, since loss of either induces a low penetrance of mild palate closure defects, while loss of both causes severe CP with a frequency similar to Afdn loss. Finally, expression of the human disease mutant NECTIN1W185X causes CP with greater penetrance than Nectin1 loss, suggesting this alteration may drive CP via a dominant interfering mechanism.<\/jats:p>","DOI":"10.1242\/dev.189241","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T18:52:06Z","timestamp":1592506326000},"source":"Crossref","is-referenced-by-count":17,"title":["Disruption of the nectin-afadin complex recapitulates features of the human cleft lip\/palate syndrome CLPED1"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9663-6983","authenticated-orcid":false,"given":"Kendall J.","family":"Lough","sequence":"first","affiliation":[{"name":"Departments of Pathology & Laboratory Medicine and Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4827-1857","authenticated-orcid":false,"given":"Danielle C.","family":"Spitzer","sequence":"additional","affiliation":[{"name":"Departments of Pathology & Laboratory Medicine and Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby J.","family":"Bergman","sequence":"additional","affiliation":[{"name":"Departments of Pathology & Laboratory Medicine and Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica J.","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of Pathology & Laboratory Medicine and Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Byrd","sequence":"additional","affiliation":[{"name":"Departments of Pathology & Laboratory Medicine and Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC, USA"},{"name":"Department of Oral & Craniofacial Health Sciences, The University of North Carolina School of Dentistry, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9975-7334","authenticated-orcid":false,"given":"Scott E.","family":"Williams","sequence":"additional","affiliation":[{"name":"Departments of Pathology & Laboratory Medicine and Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042700575509200_DEV189241C1","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1242\/dev.01125","article-title":"Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development","volume":"131","author":"Andl","year":"2004","journal-title":"Development"},{"key":"2021042700575509200_DEV189241C2","doi-asserted-by":"publisher","first-page":"3509","DOI":"10.1093\/hmg\/ddn243","article-title":"The cell adhesion molecule nectin-1 is critical for normal enamel formation in mice","volume":"17","author":"Barron","year":"2008","journal-title":"Hum. 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