{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:48:58Z","timestamp":1787021338609,"version":"build-2736575974"},"reference-count":38,"publisher":"The Company of Biologists","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,2,15]]},"abstract":"<jats:p>Clefting of the soft palate occurs as a congenital defect in humans and adversely affects the physiological function of the palate. However, the molecular and cellular mechanism of clefting of the soft palate remains unclear because few animal models exhibit an isolated cleft in the soft palate. Using three-dimensional microCT images and histological reconstruction, we found that loss of TGF\u03b2 signaling in the palatal epithelium led to soft palate muscle defects in Tgfbr2fl\/fl;K14-Cre mice. Specifically, muscle mass was decreased in the soft palates of Tgfbr2 mutant mice, following defects in cell proliferation and differentiation. Gene expression of Dickkopf (Dkk1 and Dkk4), negative regulators of WNT-\u03b2-catenin signaling, is upregulated in the soft palate of Tgfbr2fl\/fl;K14-Cre mice, and WNT-\u03b2-catenin signaling is disrupted in the palatal mesenchyme. Importantly, blocking the function of DKK1 and DKK4 rescued the cell proliferation and differentiation defects in the soft palate of Tgfbr2fl\/fl;K14-Cre mice. Thus, our findings indicate that loss of TGF\u03b2 signaling in epithelial cells compromises activation of WNT signaling and proper muscle development in the soft palate through tissue-tissue interactions, resulting in a cleft soft palate. This information has important implications for prevention and non-surgical correction of cleft soft palate.<\/jats:p>","DOI":"10.1242\/dev.103093","type":"journal-article","created":{"date-parts":[[2014,2,4]],"date-time":"2014-02-04T07:25:39Z","timestamp":1391498739000},"page":"909-917","source":"Crossref","is-referenced-by-count":48,"title":["TGF\u03b2 regulates epithelial-mesenchymal interactions through WNT signaling activity to control muscle development in the soft palate"],"prefix":"10.1242","volume":"141","author":[{"given":"Jun-ichi","family":"Iwata","sequence":"first","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA."},{"name":"Center for Craniofacial Research, Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, TX 77054, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Yokota","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thach-Vu","family":"Ho","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Pelikan","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Urata","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA."},{"name":"Division of Plastic Surgery, Children\u2019s Hospital Los Angeles, Los Angeles, CA 90027, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A.","family":"Sanchez-Lara","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA."},{"name":"Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA."},{"name":"Division of Medical Genetics, Children\u2019s Hospital Los Angeles, Los Angeles, CA 90027, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chai","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042607553673000_R1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/j.1365-2273.2004.00886.x","article-title":"Why do we have a uvula?: literature review and a new theory","volume":"29","author":"Back","year":"2004","journal-title":"Clin. 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