Integrins are heterodimeric cell surface receptors for the extracellular matrix (ECM). In epithelial ceils they serve to adhere the basal surface of the cell to the basement membrane; a3b1 integrin is a receptor for laminin, a major component of basement membranes. Our studies over the past three years have identified novel roles for a3b1 integrin. However, a3b1 integrin is also found at lateral cell membranes, a location inconsistent with its function as a receptor for the ECM. We have now demonstrated that a3b1 integrin is also a component of the cadherin:catenin complex, and that the interaction of a3b1 with CD151, a member of the tetraspanin family, is required to stimulate cadherin-mediated cell-cell adhesion. We now propose to examine the significance of the integrin:tetraspanin interaction in vivo during kidney development. We have also derived a conditional mutation of the a3 integrin gene. This has been successful, and we are now breeding these mice with several Cre recombinase-expressing mice, to study the role of a3b1 integrin in specific cell types during development and tumorigenesis. Specific Aim 1: To study coordinate signaling mediated by a3bl integrin and associated complexes. Hypothesis: Distinct signaling pathways are activated by alternative and possibly competitive association of a3b1 integrin with the cadherin:catenin complex or with RTKs. Specific Aim 2: To examine the role of integrin-dependent Writ signaling in epithelial morphogenesis. Specific Aim 3: To determine the requirement for a3b1 integrin:tetraspanin interaction in morphogenesis of the collecting system.