{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:47:23Z","timestamp":1790970443553,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["R15GM122030\u201001"],"award-info":[{"award-number":["R15GM122030\u201001"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p><jats:bold><jats:styled-content>Background:<\/jats:styled-content><\/jats:bold> Interferon regulatory factor 6 (<jats:italic>IRF6<\/jats:italic>) plays a critical role in embryonic tissue development, including differentiation of epithelial cells. Besides orofacial clefting due to haploinsufficiency of IRF6, recent human genetic studies indicated that mutations in <jats:italic>IRF6<\/jats:italic> are linked to small mandible and digit abnormalities. The function of IRF6 has been well studied in oral epithelium; however, its role in craniofacial skeletal formation remains unknown. In this study, we investigated the role of <jats:italic>Irf6<\/jats:italic> in craniofacial bone development using comparative analyses between wild\u2010type (WT) and <jats:italic>Irf6<\/jats:italic>\u2010null littermate mice. <jats:bold><jats:styled-content>Results:<\/jats:styled-content><\/jats:bold> Immunostaining revealed the expression of IRF6 in hypertrophic chondrocytes, osteocytes, and bone matrix of craniofacial tissues. Histological analysis of <jats:italic>Irf6<\/jats:italic>\u2010null mice showed a remarkable reduction in the number of lacunae, embedded osteocytes in matrices, and a reduction in mineralization during bone formation. These abnormalities may explain the decreased craniofacial bone density detected by micro\u2010CT, loss of incisors, and mandibular bone abnormality of <jats:italic>Irf6<\/jats:italic>\u2010null mice. To validate the autonomous role of IRF6 in bone, extracted primary osteoblasts from calvarial bone of WT and <jats:italic>Irf6<\/jats:italic>\u2010null pups showed no effect on osteoblastic viability and proliferation. However, a reduction in mineralization was detected in <jats:italic>Irf6<\/jats:italic>\u2010null cells. <jats:bold><jats:styled-content>Conclusions:<\/jats:styled-content><\/jats:bold> Altogether, these findings suggest an autonomous role of <jats:italic>Irf6<\/jats:italic> in regulating bone differentiation and mineralization. <jats:italic>Developmental Dynamics<\/jats:italic> 248:221\u2010232, 2019. \u00a9 2019 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.13","type":"journal-article","created":{"date-parts":[[2019,1,26]],"date-time":"2019-01-26T08:34:01Z","timestamp":1548491641000},"page":"221-232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A cleft lip and palate gene, <i>Irf6<\/i>, is involved in osteoblast differentiation of craniofacial bone"],"prefix":"10.1002","volume":"248","author":[{"given":"Jake","family":"Thompson","sequence":"first","affiliation":[{"name":"Center for Craniofacial 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