The objective of this project is to understand the molecular mechanisms by which genes for connective tissue proteins are regulated and expressed during normal development and in disease states. The formation of extracellular matrix is intimately associated with cell differentiation and tissue development in mammalian embryogenesis. Furthermore, alterations of extracellular matrix structure are associated with human conditions such as neoplastic disease and diabetes. We are studying genetic mechanisms controlling the expression and function of cartilage and basement membrane components. Recombinant DNA techniques have been used to prepare molecular clones of genes and mRNA for various cartilage and basement membrane constituents. Using these molecular tools, the genetic mechanism(s) controlling the expression of the genes has been studied. The structure of some of these constituents has been determined by cDNA sequencing. Relationships between the structure and function of the proteins have been studied using synthetic peptides deduced from cDNA sequence. Sequences in these genes regulating their expression are being studied.