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 from cartilage, salivary cells form glands, etc. Our goal is to define the molecular and cellular events involved in this process. Our approach has been (1) to identify the biologically active matrix components, (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. Estrogens have been found to promote leukocyte adhesion to endothelial cell monolayers via an increase in endothelial cell selectin adhesion receptors. In addition, estrogens promote endothelial cell adhesion, growth, migration and tube formation in vitro and angiogenesis in vivo. Using the endothelial cell tube assay, a new role for proteases, interferon inducible protein 10 and collagen has been defined and may have important clinical uses in vessel repair. Subtractive cDNA cloning of endothelial cells on plastic vs basement membrane has identified several novel genes as well as thymosin B4 and calmodulin as induced during differentiation into vessels. The laminin- derived peptide SIKVAV promotes neurite outgrowth and binds a nucleolar protein which may shuttle to the nucleolus. Another active site LAVQLSIR on laminin has been identified for neurite outgrowth. These studies demonstrate cell type-specific responses to laminin domains.