{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:37:13Z","timestamp":1790116633531,"version":"4.0.1"},"reference-count":86,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T00:00:00Z","timestamp":1561507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T00:00:00Z","timestamp":1561507200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T00:00:00Z","timestamp":1561507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NRF-NRFF2016-01"],"award-info":[{"award-number":["NRF-NRFF2016-01"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Goh Foundation"},{"name":"Duke-NUS Medical School Singapore"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Alternative splicing (AS) creates proteomic diversity from a limited size genome by generating numerous transcripts from a single protein-coding gene. Tissue-specific regulators of AS are essential components of the gene regulatory network, required for normal cellular function, tissue patterning, and embryonic development. However, their cell-autonomous function in neural crest development has not been explored. Here, we demonstrate that splicing factor Rbfox2 is expressed in the neural crest cells (NCCs), and deletion of Rbfox2 in NCCs leads to cleft palate and defects in craniofacial bone development. RNA-Seq analysis revealed that Rbfox2 regulates splicing and expression of numerous genes essential for neural crest\/craniofacial development. We demonstrate that Rbfox2-TGF-\u03b2-Tak1 signaling axis is deregulated by Rbfox2 deletion. Furthermore, restoration of TGF-\u03b2 signaling by Tak1 overexpression can rescue the proliferation defect seen in Rbfox2 mutants. We also identified a positive feedback loop in which TGF-\u03b2 signaling promotes expression of Rbfox2 in NCCs.<\/jats:p>","DOI":"10.7554\/elife.45418","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T08:00:16Z","timestamp":1561536016000},"source":"Crossref","is-referenced-by-count":43,"title":["Neural crest-specific deletion of Rbfox2 in mice leads to craniofacial abnormalities including cleft palate"],"prefix":"10.7554","volume":"8","author":[{"given":"Dasan Mary","family":"Cibi","sequence":"first","affiliation":[{"name":"Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masum M","family":"Mia","sequence":"additional","affiliation":[{"name":"Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamini","family":"Guna Shekeran","sequence":"additional","affiliation":[{"name":"Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lim Sze","family":"Yun","sequence":"additional","affiliation":[{"name":"National Heart Research Institute, National Heart Center, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reddemma","family":"Sandireddy","sequence":"additional","affiliation":[{"name":"Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Gupta","sequence":"additional","affiliation":[{"name":"Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monalisa","family":"Hota","sequence":"additional","affiliation":[{"name":"Program in 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