We have recently identified the Drosophila receptor Dscam and shown that it is essential for the formation of proper connectivity in the fly nervous system. Dscam is a member of the immunoglobulin superfamily and is highly related to the human protein "Down syndrome cell adhesion molecule" (DSCAM). The Drosophila Dscam gene is extraordinarily complex and can generate some 38,000-protein isoforms through alternative splicing. The overall goal of our studies is to test the hypothesis that alternative splice isoforms of the Dscam receptor constitute a molecular recognition code for synaptic specificity. We will use genetic and molecular approaches to functionally test the importance of neuronal receptor diversity. We propose that the extraordinary molecular diversity of Dscam provides a paradigmatic and genetically accessible case for systematically dissecting the mechanism by which neuronal receptors contribute to synaptic specificity.