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The craniofacial and dental manifestation of Robinow syndrome is heterogenous, as is the effect of altered Wnt5a in animal models. The relationship between Wnt5a and craniofacial and dental phenotypes is not fully understood. To investigate the role of Wnt5a in bone during craniofacial and dental development, we utilized a Wnt5a conditional loss-of-function (LOF: Wnt5afl\/fl;Ctskcre) and a Wnt5a conditional gain-of-function (GOF: Rosa26-LSL-Wnt5a;Ctskcre) model to determine the effect of both LOF and GOF of Wnt5a in bone cells during craniofacial and dental development. Postnatal day 10 conditional LOF Wnt5a, GOF Wnt5a, and control skulls were scanned by micro-CT and assessed using traditional and geometric morphometrics. Mandibular bone apoptosis was further assessed by TUNEL staining. Conditional Wnt5a LOF resulted in midface hypoplasia, increased maxillary intermolar width, increased rostral basisphenoid width, and delayed molar eruption. Wnt5a LOF mandibles did not have altered BMD or bone microarchitecture unlike our previous study examining Wnt5a LOF femurs. In contrast, conditional Wnt5a GOF results in macrocephaly, shortened hard palate, increased zygomatic length, micrognathia, and mandibular process dysmorphology. The micrognathia and mandibular process dysmorphology in the Wnt5a GOF mice were not due to increased apoptosis. A partially penetrant snout deviation was present in both the Wnt5a LOF and GOF mice. Craniofacial and dental phenotype differed between mice with conditional GOF and LOF of Wnt5a, consistent with the craniofacial phenotype heterogeneity in WNT5A-associated Robinow syndrome. We detected tooth eruption delay, mandibular condyle dysmorphology, and facial asymmetry in mice with altered Wnt5a that have not been previously reported in patients with WNT5A-associated Robinow syndrome. Our data suggest precise regulation of Wnt5a is essential for proper craniofacial and dental development.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziag060","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T11:45:30Z","timestamp":1775216730000},"source":"Crossref","is-referenced-by-count":0,"title":["Wnt5a gain- and loss-of-function in bone have distinct craniofacial phenotypes"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2003-4625","authenticated-orcid":false,"given":"Claire J","family":"Houchen","sequence":"first","affiliation":[{"name":"School of Dentistry, University of Missouri-Kansas City , Kansas City, MO 64108 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Portia","family":"Hahn Leat","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of Missouri-Kansas City , Kansas City, MO 64108 ,","place":["United 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L","family":"Roberts","sequence":"additional","affiliation":[{"name":"Emory School of Medicine, Emory University , Atlanta, GA 30322,","place":["United States"]},{"name":"College of Health Solutions, Arizona State University , Phoenix, AZ 85004 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3322-281X","authenticated-orcid":false,"given":"Hicham","family":"Drissi","sequence":"additional","affiliation":[{"name":"Emory School of Medicine, Emory University , Atlanta, GA 30322,","place":["United States"]},{"name":"Atlanta VA Medical Center , Decatur, GA 30033 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-7808","authenticated-orcid":false,"given":"Erin E","family":"Bumann","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of Missouri-Kansas City , Kansas City, MO 64108 ,","place":["United 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