Recent work from the laboratory of Dr. Patterson as well as from other research groups has identified several secreted and cell surface molecules which may be involved in the intercellular interactions mediating axon growth and synapse formation. The goal of this project is to determine the functional role in neuronal development and regeneration of one of these sets of molecules . proteolytic enzymes or proteases. Dr. Patterson and his colleagues have biochemically characterized several proteases, including plasminogen activator, which are spontaneously released by the distal tips of growing neurites in culture. In addition, these researchers have partially characterized two irreversible plasminogen activator inhibitors which are released by muscle and peripheral glial cultures. Recent evidence from Dr. Patterson's lab has shown that inhibition of plasminogen activator can increase the rate of neurite outgrowth in culture. The proposed work will extend these studies to an in viv o (rat and chick) preparation. The experimental strategy is to use antibodies to perturb the activity of this protease and observe the effect on regenerating peripheral and central nerves in the intact animal. The establishment of complex synaptic arrays during vertebrate neural development is the result of an equally complex series of cellular interactions between neurons and their targets. These interactions occur throughout the various stages of cell migration, axonal outgrowth, recognition of target cells, differentiation of synaptic elements, and reorganization and maintenance of final connections. This research will contribute to our understanding of the role of proteases in axonal outgrowth during development and regeneration in the nervous system.
