This application proposes a five year educational program at Baylor College of Dentistry, Texas A and M University System (BCD) for Mr. David Erik Kern. This program will combine Ph.D. studies in Biomedical Sciences with concurrent clinical training leading to a D.D.S. Mr. Kern's ultimate goal is a career in dental research and academic dentistry. His research interests are directed toward cartilage development and the genetic basis for chondrodysplasias, craniofacial abnormalities, and other genetic defects in human cartilage and bone development. A tentative research proposal is outlined, that will be modified as Erik begins the research component of the training. The research will address hypotheses concerning the cell-extracellular matrix interactions that are important for chondrocyte survival, proliferation and terminal differentiation. In previous work my group developed an organ culture model in which chondrocytes recapitulate normal development in their natural microenvironment. We have previously shown that sterna cultured with blocking integrin antibodies have decreased growth, survival, differentiation, and type X collagen secretion. This project builds on the previous work to further characterize the effects of cell-matrix interactions on collagen and other secreted protein synthesis and mRNA expression. Erik will specifically ask: How is type X collagen down regulated when cell-matrix interactions are blocked? Are other collagen (II, IX or XI) expression or synthesis affected by blocking cell-ECM interactions with integrin antibodies? Do other matrix proteins or molecules (cartilage matrix proteins, proteoglycans, or annexin V) change expression or synthesis in presence of blocking integrin antibodies? Do integrins themselves change expression or synthesis in the presence of blocking antibodies? Techniques will include maintaining whole cartilage in organ culture, immunoprecipitation, Western Blots, RNA extraction, Northern Blots, in situ hybridization, immunohistochemistry, and confocal microscopy.