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Defects can only be corrected surgically and require complex life-long treatments. Our studies utilized the well-characterized Pax9\u2212\/\u2212 mouse model with a consistent cleft palate phenotype to test small-molecule Wnt agonist therapies. We show that the absence of Pax9 alters the expression of Wnt pathway genes including Dkk1 and Dkk2, proven antagonists of Wnt signaling. The functional interactions between Pax9 and Dkk1 are shown by the genetic rescue of secondary palate clefts in Pax9\u2212\/\u2212Dkk1f\/+;Wnt1Cre embryos. The controlled intravenous delivery of small-molecule Wnt agonists (Dkk inhibitors) into pregnant Pax9+\/\u2212 mice restored Wnt signaling and led to the growth and fusion of palatal shelves, as marked by an increase in cell proliferation and osteogenesis in utero, while other organ defects were not corrected. This work underscores the importance of Pax9-dependent Wnt signaling in palatogenesis and suggests that this functional upstream molecular relationship can be exploited for the development of therapies for human cleft palates that arise from single-gene disorders.<\/jats:p>","DOI":"10.1242\/dev.157750","type":"journal-article","created":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T20:11:01Z","timestamp":1505160661000},"page":"3819-3828","source":"Crossref","is-referenced-by-count":70,"title":["Small-molecule Wnt agonists correct cleft palates in\n                    <i>Pax9<\/i>\n                    mutant mice\n                    <i>in utero<\/i>"],"prefix":"10.1242","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-4291","authenticated-orcid":false,"given":"Shihai","family":"Jia","sequence":"first","affiliation":[{"name":"S 1 , , Salt Lake City, UT 84112 , USA"},{"name":"chool of Dentistry 1 , , Salt Lake City, UT 84112 , USA"},{"name":"University of Utah 1 , , Salt Lake City, UT 84112 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"S 1 , , Salt Lake City, UT 84112 , USA"},{"name":"chool of Dentistry 1 , , Salt Lake City, UT 84112 , USA"},{"name":"University of Utah 1 , , Salt Lake City, UT 84112 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Fanelli","sequence":"additional","affiliation":[{"name":"S 1 , , Salt Lake City, UT 84112 , USA"},{"name":"chool of Dentistry 1 , , Salt Lake City, UT 84112 , USA"},{"name":"University of Utah 1 , , Salt Lake City, UT 84112 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinshen","family":"Wee","sequence":"additional","affiliation":[{"name":"S 1 , , Salt Lake City, UT 84112 , USA"},{"name":"chool of Dentistry 1 , , Salt Lake City, UT 84112 , USA"},{"name":"University of Utah 1 , , Salt Lake City, UT 84112 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bonds","sequence":"additional","affiliation":[{"name":"Texas A&M University College of Dentistry 2 Department of Biomedical Sciences , , Dallas, TX 75246 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Schneider","sequence":"additional","affiliation":[{"name":"University of Lausanne 3 Department of Biochemistry , , CH-1066 Epalinges , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1097-8582","authenticated-orcid":false,"given":"Gabriele","family":"Mues","sequence":"additional","affiliation":[{"name":"Texas A&M University College of Dentistry 2 Department of Biomedical Sciences , , Dallas, TX 75246 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1505-5173","authenticated-orcid":false,"given":"Rena N.","family":"D'Souza","sequence":"additional","affiliation":[{"name":"S 1 , , Salt Lake City, UT 84112 , USA"},{"name":"chool of Dentistry 1 , , Salt Lake City, UT 84112 , USA"},{"name":"University of Utah 1 , , Salt Lake City, UT 84112 , USA"},{"name":"School of Medicine, University of Utah 4 Departments of Neurobiology & Anatomy, Pathology , , Salt Lake City, UT 84112 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061215574610200_DEV157750C1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1471-213X-14-3","article-title":"Neural crest-specific deletion of Ldb1 leads to cleft secondary palate with impaired palatal shelf elevation","volume":"14","author":"Almaidhan","year":"2014","journal-title":"BMC Dev. 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