During embryonic development of the peripheral nervous system, migrating neurons and their advancing growth cones must traverse and penetrate a variety of extracellular impediments to reach their targets. The secretion of proteases, including plasminogen activators, are thought to facilitate movement of neurons and their growth cones by locally digesting impeding cell-cell and cell- matrix components. To study this process, developmental changes in the genetic expression of plasminogen activators will be studied in mouse sensory ganglia in vivo and in cell culture. Molecular probes will be used to study the type of cells synthesizing plasminogen activators as well as possible regulation of plasminogen activator expression by various growth factors. The role of plasminogen activators in axonal growth will be assessed by blocking synthesis with antisense oligonucleotides. These studies are important not only for increasing our understanding of the mechanisms underlying normal neuronal development, but also those that may play a role during regeneration of peripheral nerves in the mammal.
