Cartilage is a highly specialized connective tissue consisting of a sparse number of chondrocytic cells embedded in an extensive extracellular matrix. The biomechanical characteristics of the cartilage extracellular matrix are particularly suited to bearing a compressive load. The purpose of this project is to understand the structure and function of cartilage components and to identify the mechanisms underlying cartilage formation. We have also initiated a genome project to identify genes crucial for craniofacial and tooth development. Collagen II is a major fibrillar collagen in cartilage. We previously identified an enhancer in the first intron of the collagen II gene which increased transcription of the gene. We have identified a promoter element located close to the transcription initiation site which requires the enhancer-mediated transcription of the type II collagen gene. We have identified a 100 bp sequence as the minimum size of the enhancer which contained several sequence motifs homologous to the regulatory region of the link protein gene. We have cloned several protein factors bound to the enhancer. One of them is the C-propeptide of type II collagen. Our results suggest that the C- propeptide down-regulates the transcription of the type II collagen gene through negative feedback mechanisms. We have identified an enhancer of the link protein gene. This region contains a sequence homologous to the enhancer sequence of the collagen II gene and suggests that a common factor is involved in coordinate transcription of both link protein and collagen II genes in chondrocytes. A genome project for craniofacial and tooth development has been initiated in collaboration with the Developmental Mechanisms Section. The goal of this project is to understand the molecular mechanisms underlying craniofacial and tooth development. We have identified a novel gene specific to ameloblasts from the incisor cDNA library. We named this new gene product """"""""ameloblastin"""""""" because its expression is specific to ameloblasts. Expression of ameloblastin mRNA is most intense in secretory-stage ameloblasts, similar to amelogenin mRNA. Ameloblastin mRNA is also expressed in premature stage ameloblasts and in retrogressive ameloblasts where amelogenin mRNA is rarely expressed.
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