{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:46:45Z","timestamp":1783122405807,"version":"3.54.6"},"reference-count":52,"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":["R56-DE024749"],"award-info":[{"award-number":["R56-DE024749"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Cleft lip is one of the most common human birth defects. However, there remain a limited number of mouse models of cleft lip that can be leveraged to characterize genes and mechanisms that cause this disorder. While crosstalk between epithelial and mesenchymal cells underlies formation of the face and palate, the basic molecular events mediating this crosstalk remain poorly understood. We previously demonstrated that mice lacking epithelial-specific splicing factor Esrp1 have fully penetrant bilateral CL\/P. In this study we further investigated the mechanisms leading to cleft lip as well as cleft palate in both existing and new Esrp1 mutant mouse models. These studies included a detailed transcriptomic analysis of changes in ectoderm and mesenchyme in Esrp1\u2212\/- embryos during face formation. We identified altered expression of genes previously implicated in cleft lip and\/or palate, including components of multiple signaling pathways. These findings provide the foundation for detailed investigations using Esrp1 mutant disease models to examine gene regulatory networks and pathways that are essential for normal face and palate development and whose disruption leads to orofacial clefting in human patients.<\/jats:p>","DOI":"10.1242\/dev.187369","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T17:25:12Z","timestamp":1586193912000},"source":"Crossref","is-referenced-by-count":42,"title":["Cleft lip and cleft palate (CL\/P) in\n                    <i>Esrp1<\/i>\n                    KO mice is associated with alterations in epithelial-mesenchymal crosstalk"],"prefix":"10.1242","author":[{"given":"SungKyoung","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Sears","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA"},{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Biology, University of Colorado School of Dental, Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imad","family":"Salhab","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Krebs","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Bern, Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xing","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA"},{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Duck","family":"Nah","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Biology, University of Colorado School of Dental, Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8083-0412","authenticated-orcid":false,"given":"Russ P.","family":"Carstens","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA"},{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042700553392400_DEV187369C1","doi-asserted-by":"publisher","first-page":"e08954","DOI":"10.7554\/eLife.08954","article-title":"The splicing regulators Esrp1 and Esrp2 direct an epithelial splicing program essential for mammalian development","volume":"4","author":"Bebee","year":"2015","journal-title":"eLife"},{"key":"2021042700553392400_DEV187369C2","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1038\/onc.2013.50","article-title":"The RNA-binding protein Rbfox2: an essential regulator of EMT-driven alternative splicing and a mediator of cellular invasion","volume":"33","author":"Braeutigam","year":"2014","journal-title":"Oncogene"},{"key":"2021042700553392400_DEV187369C3","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.devcel.2005.05.016","article-title":"Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system","volume":"9","author":"Carroll","year":"2005","journal-title":"Dev. 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