Investigations will be directed at elucidating the biochemical nature of cell-cell interactions that influence development and differentiation in th central nervous system. Reaggregate and surface cultures of neonatal mouse cerebellum will be used to monitor biochemical and morphological developmen . The role of extracellular proteases, primarily plasminogen activator, in granule cell migration will be examined both in vitro and in vivo using specific proteolytic inhibitors and antibodies to murine tissue plasminogen activator. Tissue plasminogen activator gene transcription will be monitore during cerebellar development and a newly proposed neuronal cell surface receptor for tissue plasminogen activator will be characterized. The action of extracellular proteases appears to be an important mechanism to facilita e cell and axonal growth cone migration during embryogenesis and neural histogenesis, and its regulation may have important consequences for neural regeneration.
