DESCRIPTION: The long term goal of the proposal is to understand how the specific patterns of synaptic connectivity between neurons are established. The orderliness of this process is crucial as mistakes in connectivity can disrupt neural circuits, and block proper function of the nervous system in all organisms including man. How neurons select their synaptic partners at a molecular level remains largely unsolved. The applicant and his colleagues will apply molecular, genetic, and electrophysiological methods to directly assay genes that function in the process of establishing synaptic connections. In this project, they will focus on the sensory nervous system of adult Drosophila. They have characterized a set of enhancer trap insertion lines that are expressed in specific subsets of sensory axons. Mutations caused by the insertion or excision of the P element will be characterized to determine the nature of the defects they cause in neuronal differentiation. Characterization of the genes identified by these insertions may aid in the understanding of the molecular processes that establish specific patterns of synaptic connections. Cloning and sequencing of the relevant genes will provide a description of their products. Finally, anatomical and electrophysiological assays for the function of the genes will be developed. Since many of the genes will be common to humans and flies, the identification of these genes may prove to be of clinical relevance.