The mammalian brain, composed of 1011 nerve cells with 1014 precise synaptic interconnections, is an organ of unparalleled complexity. A major challenge in modern neuroscience is to elucidate the mechanisms by which nascent neurons form and maintain this elaborate cellular network, thereby providing critical insights into neural circuit formation during development and repair following injury. A key initial step in the establishment of neuronal network is the outgrowth of neurites, a complex process that requires coordinated cytoskeleton remodeling and vesicle targeting to designated plasma membrane domains. The research goal of our lab is to use a multi-disciplinary approach to define the biochemical events underlying neurite outgrowth. We have identified two protein complexe, the exocyst (rsec6/8) complex and the sep2/4/6/7/8 family, required for promoting and regulating neurite outgrowth. Currently, we are using molecular biological, biochemical, immunochemical, electrophysiological and cell biological techniques to investigate the molecular mechanisms of these two complexes in regulating neurite developmen, axon/dendritic differentiation and synapse formation. In addition. we are using these two complexes as molecular handles to identify and isolate other protein players in the neurite outgrowth process. Elucidation of the molecular events underlying neurite outgrowth should provide important insights into the regulation of neuronal growth, differentiation and regeneration.