The bone morphogenetic proteins (BMPs) are involved in a variety of developmental and differentiation processes in skin and hair, heart, kidney, reproductive tissues, neural tissues and cartilage, bone and tooth development. In this application, the investigators' major goal is to characterize the mechanisms by which transcription of the BMP2 and BMP4 genes are regulated in osteoblasts and other tissues in vivo and to examine the mechanisms by which BMP2 affects osteoblast function. The stated goals are: 1. To extend prior studies on BMP effects on osteoblasts and chondroblasts and in particular to identify homeobox and other mRNA species which are regulated by BMP2 and which may regulate BMP2 and BMP4 expression during differentiation. 2. To characterize transcriptional regulation of the BMP2 and BMP4 genes in vivo, they will use transgenic mice in which BMP2 or BMP4 gene fragments from the 5' flanking region and other regions are linked to bacterial beta-galactosidase (LacZ) and/or luciferase (LUC). BMP2 and 4 gene transcription control will be examined. Using these mice, genetic crosses to candidate mutant mice can be established to evaluate gene networks and interactions with the BMP2 and BMP4 genes. 3. Using specific regions of the BMP4 promoter driving human BMP4 cDNA that directs expression in the normal BMP4 domains of 6.5-8.5 dpc embryos, the investigators will attempt to rescue the BMP4 homozygous null mutant phenotype. New phenotypes may develop that will give insight into the role of BMP4 later in development.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Special Emphasis Panel (ZRG4-GRM (03))
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University of Texas Health Science Center San Antonio
Internal Medicine/Medicine
Schools of Medicine
San Antonio
United States
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Yang, Wuchen; Guo, Dayong; Harris, Marie A et al. (2013) Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells. J Cell Sci 126:4085-98
Yang, Wuchen; Harris, Marie A; Heinrich, Jelica Gluhak et al. (2009) Gene expression signatures of a fibroblastoid preosteoblast and cuboidal osteoblast cell model compared to the MLO-Y4 osteocyte cell model. Bone 44:32-45
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Xu, S C; Harris, M A; Rubenstein, J L et al. (2001) Bone morphogenetic protein-2 (BMP-2) signaling to the Col2alpha1 gene in chondroblasts requires the homeobox gene Dlx-2. DNA Cell Biol 20:359-65
Ghosh-Choudhury, N; Choudhury, G G; Harris, M A et al. (2001) Autoregulation of mouse BMP-2 gene transcription is directed by the proximal promoter element. Biochem Biophys Res Commun 286:101-8

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