A large collection of clonal nerve and glial cell lines will be used in conjunction with primary cultures to examine problems related to the development of the nervous system. The roles of extracellular macromolecules in the regulation of nerve and glial cell division and differentiation will be defined. Emphasis will be placed in three areas. The first is the further characterization of Schwannoma derived growth factor (SDGF) and PDGF-associated protein (PAP), two proteins recently isolated and cloned in our laboratory. The tissue distribution of these proteins will be studied in the developing rat and primary cultures from areas which express these proteins will be used to study their biological function. The second major effort will be to isolate novel CNS mitogens and neurotrophic proteins from a newly established collection of clonal cell lines from the rat eye. Both well defined and novel biological assays will be used to purify the proteins, and their partial amino acid sequencing will lead to their cloning and expression. Finally, the role of extracellular molecules in the regulation of Schwann cell division will be studied in primary culture systems. Experiments are outlined to identify through the use of antisense and antibody technology, and by expression cloning, the growth factors and their receptors which modulate Schwann cell mitosis during development. The experiments in this proposal should help define the role of protein growth factors in the developing nervous system. Hopefully, this information will lead to a treatment for some neurodegenerative diseases and CNS trauma.
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