Cartilage is a highly specialized connective tissue with distinct morphological and biochemical characteristics. Histologically, it contains chondrocytes surrounded by extensive extracellular matrix. In development, cartilage serves as the template for the formation of skeleton, and it lines the joint surface. In adults, the collagen network in cartilage provides a scaffolding for proteoglycans in the extracellular matrix and confers tensile strength, which is important for resisting compression and shearing loads. Chondrocytes produce large amounts of cartilage-specific matrix molecules, including type II collagen, aggrecan, link protein, and hyaluronan. Hormones and vitamins affect cartilage development and maturation by regulating the transcription of genes. Our objective is to define the mechanisms for activating chondrocyte-specific genes and to elucidate the molecular basis of cartilage development. Using an animal model, we also study the function of cartilage proteins in vivo. We initiated the Oral and Craniofacial Genome Anatomy Project (OC-GAP) to identify novel genes important for tooth and craniofacial development. Our goal is to discover and characterize previously unknown genes in order to understand how tooth and craniofacial tissues develop and to define the molecular defects underlying anomalies of these tissues and oral cancer. Craniofacial anomalies and cancer of the mouth, neck, and head are of major public concern. A large number of genes are believed to be involved in such anomalies and cancers. As an initial step, we have started to identify and catalogue the genes involved in specific stages of tooth and craniofacial development. The identification of genes that have highly location- and stage-specific expression is important, because the gene products are likely to have key roles in the formation of craniofacial tissues. Because mutations in these genes probably cause craniofacial anomalies and cancer, this information will be useful for generating diagnostic reagents, developing methods for disease and birth- defect prevention, and for potential gene therapies. - Cartilage, craniofacial development, gene regulation
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