Synapse formation occurs principally during nervous system development. However, in response to injury new synapses can be formed both in the peripheral nervous system and to a more limited extent in the central nervous system (CNS) . In addition, some mature neurons within discreet CNS regions are able to undergo restructuring of their synapses in response to changes in their environment. This property of mature neuronsis often referred to as synaptic plasticity and may serve as the basis for memory formation and sexually dimorphic physiology. The mechanisms that regulate these diverse forms of synapse formation are probably different, but all involve the highly regulated expression of specialized neuronal gene products. One such neural gene product, termed GAP-43, has been implicated in these varied forms of synaptogenesis. Our program is devoted to elucidating the molecular mechanisms involved in the regulation of synapse formation. The approach is to define the mediators and mechanisms that regulate gene expression during synaptogenesis. We have initiated this work by characterizing the regulation of GAP-43 gene expression by nerve growth factor (NGF) and corticosteroid in cultured neurons and in pheochromocytoma cells (PC12). This application identifies three areas for further study: 1) The identification of the mechanisms responsible for NGF up-regulation and corticosteroid down-regulation of GAP-43 gene expression; 2) The examination of GAP-43 gene regulation by synapse formation with appropriate target cells; and 3) The isolation and characterization of other genes expressed during synaptogenesis.
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