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Cell Dev. Biol."],"abstract":"<jats:p>The roles of bone morphogenetic protein (BMP) signaling in palatogenesis were well documented in the developing hard palate; however, little is known about how BMP signaling regulates the development of soft palate. In this study, we overexpressed <jats:italic>Noggin<\/jats:italic> transgene via <jats:italic>Osr2-cre<\/jats:italic><jats:sup>KI<\/jats:sup> allele to suppress BMP signaling in the developing soft palate. We found that BMP-Smad signaling was detected in the palatal muscles and surrounding mesenchyme. When BMP-Smad signaling was suppressed by the overexpressed <jats:italic>Noggin<\/jats:italic>, the soft palatal shelves were reduced in size with the hypoplastic muscles and the extroversive hypophosphatasia (HPP). The downregulated cell proliferation and survival in the <jats:italic>Osr2-cre<\/jats:italic><jats:sup>KI<\/jats:sup><jats:italic>;pMes-Noggin<\/jats:italic> soft palates were suggested to result from the repressed <jats:italic>Shh<\/jats:italic> transcription and Gli1 activity, implicating that the BMP-Shh-Gli1 network played a similar role in soft palate development as in the hard palate. The downregulated Sox9, <jats:italic>Tenascin-C<\/jats:italic> (<jats:italic>TnC<\/jats:italic>), and <jats:italic>Col1<\/jats:italic> expression in <jats:italic>Osr2-cre<\/jats:italic><jats:sup>KI<\/jats:sup><jats:italic>;pMes-Noggin<\/jats:italic> soft palate indicated the impaired differentiation of the aponeurosis and tendons, which was suggested to result in the hypoplasia of palatal muscles. Intriguingly, in the <jats:italic>Myf5-cre<\/jats:italic><jats:sup>KI<\/jats:sup><jats:italic>;pMes-Noggin<\/jats:italic> and the <jats:italic>Myf5-cre<\/jats:italic><jats:sup>KI<\/jats:sup><jats:italic>;Rosa26R-DTA<\/jats:italic> soft palates, the hypoplastic or abrogated muscles affected little the fusion of soft palate. Although the <jats:italic>Scx<\/jats:italic>, <jats:italic>Tnc<\/jats:italic>, and <jats:italic>Co1<\/jats:italic> transcription was significantly repressed in the tenogenic mesenchyme of the <jats:italic>Myf5-cre<\/jats:italic><jats:sup>KI<\/jats:sup><jats:italic>;pMes-Noggin<\/jats:italic> soft palate, the Sox9 expression, and the <jats:italic>Tnc<\/jats:italic> and <jats:italic>Col1<\/jats:italic> transcription in aponeurosis mesenchyme were almost unaffected. It implicated that the fusion of soft palate was controlled by the mesenchymal clues at the tensor veli palatini (TVP) and levator veli palatini (LVP) levels, but by the myogenic components at the palatopharyngeus (PLP) level.<\/jats:p>","DOI":"10.3389\/fcell.2021.711334","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T06:11:29Z","timestamp":1630995089000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Noggin Overexpression Impairs the Development of Muscles, Tendons, and Aponeurosis in Soft Palates by Disrupting BMP-Smad and Shh-Gli1 Signaling"],"prefix":"10.3389","volume":"9","author":[{"given":"Jiamin","family":"Deng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Cong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.diff.2016.02.005","article-title":"Key transcription factors in the differentiation of mesenchymal stem cells.","volume":"92","author":"Almalki","year":"2016","journal-title":"Differentiation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.ydbio.2010.12.028","article-title":"Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation.","volume":"350","author":"Baek","year":"2011","journal-title":"Dev. 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