{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:20:10Z","timestamp":1791300010703,"version":"4.1.0"},"reference-count":51,"publisher":"The Company of Biologists","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,11,1]]},"abstract":"<jats:p>Cleft palate and skull malformations represent some of the most frequent congenital birth defects in the human population. Previous studies have shown that TGF\u03b2 signaling regulates the fate of the medial edge epithelium during palatal fusion and postnatal cranial suture closure during skull development. It is not understood, however, what the functional significance of TGF\u03b2 signaling is in regulating the fate of cranial neural crest (CNC)cells during craniofacial development. We show that mice with Tgfbr2conditional gene ablation in the CNC have complete cleft secondary palate,calvaria agenesis, and other skull defects with complete phenotype penetrance. Significantly, disruption of the TGF\u03b2 signaling does not adversely affect CNC migration. Cleft palate in Tgfbr2 mutant mice results from a cell proliferation defect within the CNC-derived palatal mesenchyme. The midline epithelium of the mutant palatal shelf remains functionally competent to mediate palatal fusion once the palatal shelves are placed in close contact in vitro. Our data suggests that TGF\u03b2 IIR plays a crucial, cell-autonomous role in regulating the fate of CNC cells during palatogenesis. During skull development, disruption of TGF\u03b2 signaling in the CNC severely impairs cell proliferation in the dura mater, consequently resulting in calvaria agenesis. We provide in vivo evidence that TGF\u03b2 signaling within the CNC-derived dura mater provides essential inductive instruction for both the CNC- and mesoderm-derived calvarial bone development. This study demonstrates that TGF\u03b2 IIR plays an essential role in the development of the CNC and provides a model for the study of abnormal CNC development.<\/jats:p>","DOI":"10.1242\/dev.00708","type":"journal-article","created":{"date-parts":[[2003,9,15]],"date-time":"2003-09-15T18:02:13Z","timestamp":1063648933000},"page":"5269-5280","source":"Crossref","is-referenced-by-count":325,"title":["Conditional inactivation of<i>Tgfbr2<\/i>in cranial neural crest causes cleft palate and calvaria defects"],"prefix":"10.1242","volume":"130","author":[{"given":"Yoshihiro","family":"Ito","sequence":"first","affiliation":[{"name":"Center for Craniofacial Molecular Biology School of Dentistry University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Yong","family":"Yeo","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology School of Dentistry University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Chytil","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Vanderbilt University, 22 South Pierce Avenue,PRB Room 649, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Han","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology School of Dentistry University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Pablo","family":"Bringas","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology School of Dentistry University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology School of Dentistry University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F.","family":"Shuler","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology School of Dentistry University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold L.","family":"Moses","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Vanderbilt University, 22 South Pierce Avenue,PRB Room 649, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chai","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology School of Dentistry University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042611513957700_REF1","unstructured":"Brunet, C. 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