| 0585 The Role of BMP4 in Postnatal Craniofacial and Tooth Cytodifferentiation | ||
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L.E. MARTINEZ1, W. YANG1, J. FENG2, J.-H. ZHANG3, S.E. HARRIS1, M.A. HARRIS1, and J. GLUHAK-HEINRICH4, 1U. of Texas Health Science Center at San Antonio, USA, 2University of Missouri -Kansas City, USA, 3Vanderbilt University, Nashville, TN, USA, 4University of Texas San Antonio / Health Science Ctr, USA Bone morphogenetic protein 4 (BMP4) demonstrates regulatory roles during the various stages of early head and tooth development. Little is known about the role of BMP4 in postnatal craniofacial and tooth cytodifferentiation. During tooth development, expression of BMP4 shifts from dental epithelium and mesenchyme to the enamel knot, dental papilla, and dental sac. In the late bell or cytodifferentiation stage of tooth development, pre-odontoblasts and pre-ameloblasts are formed. These cells will differentiate and carry out dentinogenesis and amelogenesis respectively in the subsequent secretory stage. The role of BMP4 in odontoblasts and ameloblasts is unknown. Objectives: To determine the phenotypic characteristics of postnatal head and tooth development (formation and mineralization) in the absence of BMP4 in osteoblasts and odontoblasts. Methods: Utilizing 3.6 collagen-Cre mice crossed with BMP4 floxed mice, functional deletion of BMP4 (by excision of exons 3-4) occurs in osteoblasts and odontoblasts of progeny. BMP4ckO mice and their sibling controls were selected for phenotypic characterization. The analytical methods employed include X-ray and histological techniques, in situ hybridization, and immunocytochemical analysis of BMP signaling and other signaling pathways. Results: BMP4 conditional knock-out (BMP4cKO) mice display reduced calvarial size and osteopenia by day 12 in alveolar bone of the mandible. Dentin thickness is reduced (20-40%) and enamel formation is delayed. Also, DMP1 expression, a marker for dentinal tubule formation by odontoblasts is reduced in teeth of 12 day BMP4 cKO Conclusions: The absence of BMP4 in early odontoblasts, as well as osteoblasts, impairs mineralization of the alveolar bone, and delays the process of dentinogenesis, as assayed by odontogenic markers. Further study will address the role of BMP4 and BMP signaling during the tooth cytodifferentiation and secretory stages. This will lead to better predictive models of genes disrupted in a variety of tooth disorders. Supported by NIDCR Grant DE14318, COSTAR.
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| Seq #87 - Cell differentiation 2:00 PM-3:15 PM, Thursday, March 22, 2007 Ernest N. Morial Convention Center Exhibit Hall I2-J | ||
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