Role of Extracellular Matrix In Cell Differentiation and Embryogenesis

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The extracellular matrix has been found to be important in embryogenesis and in tissue repair. From in vitro studies using purified components, a better understanding of how cells adhere, migrate, proliferate, and differentiate in response to tissue and cell-specific matrix molecules has been established. We have found that the basement membrane, the extracellular matrix which underlies all epithelial cells and endothelial cells and surrounds nerve cells, promotes cell differentiation in vitro. When cultured on basement membrane, endothelial cells form capillary-like structures with a lumen, chondrocytes form cartilage, salivary cells form glands, etc. Our goal is to define the molecular and cellular events involved in this process. Our approachhas been (1) to identify the biologically active matrix components, with respect to cell adhesion, migration, proliferation and differentiation, (2) localize active sites on the matrix component with synthetic peptides, (3) identify and characterize cellular receptors, (4) gain an understanding of the intracellular events involved in the biological response, and (5) identify genes induced by the extracellular matrix. We work in several in vitro model systems including primary and established tumor cells, endothelial cells, and salivary gland cells. We have used the endothelial cell tube assays in vitro and in vivo angiogenesis assays to define molecules which regulate vessel formation in development and disease. Salivary gland cells have been used to define factors important to gland development and function. Our goal is to understand how the extracellular matrix regulates tissue formation, repair, and certain pathological processes. We hope to develop both therapeutic and diagnostic agents.