{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:40:16Z","timestamp":1791322816981,"version":"4.3.1"},"reference-count":33,"publisher":"The Company of Biologists","issue":"13","license":[{"start":{"date-parts":[[1999,7,1]],"date-time":"1999-07-01T00:00:00Z","timestamp":930787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Osteoblasts and odontoblasts, cells that are responsible for the formation of bone and dentin matrices respectively, share several molecular characteristics. Recently, Cbfa1 was shown to be a critical transcriptional regulator of osteoblast differentiation. Mutations in this gene cause cleidocranial dysplasia (CCD), an autosomal dominant disorder in humans and mice characterized by defective bone formation. CCD also results in dental defects that include supernumerary teeth and delayed eruption of permanent dentition. The dental abnormalities in CCD suggest an important role for this molecule in the formation of dentition. Here we describe results of studies aimed at understanding the functions of Cbfa1 in tooth formation. RT-PCR and in situ hybridization analyses show that Cbfa1 has a unique expression pattern in dental mesenchyme from the bud to early bell stages during active epithelial morphogenesis. Unlike that observed in osteoblast differentiation, Cbfa1 is downregulated in fully differentiated odontoblasts and is surprisingly expressed in ectodermally derived ameloblasts during the maturation phase of enamel formation. The role of Cbfa1 in tooth morphogenesis is further illustrated by the misshapen and severely hypoplastic tooth organs in Cbfa1\u2212\/\u2212 mice. These tooth organs lacked overt odontoblast and ameloblast differentiation and normal dentin and enamel matrices. Epithelial-mesenchymal recombinants demonstrate that dental epithelium regulates mesenchymal Cbfa1 expression during the bud and cap stages and that these effects are mimicked by the FGFs but not by the BMPs as shown by our bead implantation assays. We propose that Cbfa1 regulates the expression of molecules in mesenchyme that act reciprocally on dental epithelium to control its growth and differentiation. Taken together, our data indicate a non-redundant role for Cbfa1 in tooth development that may be distinct from that in bone formation. In odontogenesis, Cbfa1 is not involved in the early signaling networks regulating tooth initiation and early morphogenesis but regulates key epithelial-mesenchymal interactions that control advancing morphogenesis and histodifferentiation of the epithelial enamel organ.<\/jats:p>","DOI":"10.1242\/dev.126.13.2911","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T19:38:14Z","timestamp":1619206694000},"page":"2911-2920","source":"Crossref","is-referenced-by-count":291,"title":["<i>Cbfa1<\/i> is required for epithelial-mesenchymal interactions regulating tooth development in mice"],"prefix":"10.1242","volume":"126","author":[{"given":"Rena N.","family":"D\u2019Souza","sequence":"first","affiliation":[{"name":"Department of Orthodontics 2 , Dental Branch, University of Texas Health Science Center, 6516 John Freeman Avenue, Houston, Texas 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"\u00c5berg","sequence":"additional","affiliation":[{"name":"Developmental Biology Program 1 , Institute of Biotechnology, Viikki Biocenter, FIN-00014 University of Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Gaikwad","sequence":"additional","affiliation":[{"name":"Department of Orthodontics 2 , Dental Branch, University of Texas Health Science Center, 6516 John Freeman Avenue, Houston, Texas 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Cavender","sequence":"additional","affiliation":[{"name":"Department of Orthodontics 2 , Dental Branch, University of Texas Health Science Center, 6516 John Freeman Avenue, Houston, Texas 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Owen","sequence":"additional","affiliation":[{"name":"Imperial Cancer Research Fund 3 , Lincoln\u2019s Inn Fields, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Karsenty","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics 4 , Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Thesleff*","sequence":"additional","affiliation":[{"name":"Developmental Biology Program 1 , Institute of Biotechnology, Viikki Biocenter, FIN-00014 University of Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1999,7,1]]},"reference":[{"key":"2023090607380431800_DEVELOP_126_13_2911C1","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/(SICI)1097-0177(199712)210:4&lt;383::AID-AJA3&gt;3.0.CO;2-C","article-title":"Expression patterns of BMPs in the developing mouse tooth suggests roles in morphogenesis and cell differentiation","volume":"210","author":"\u00c5berg","year":"1997","journal-title":"Dev. 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