Our long-term goals are: a) to obtain a comprehensive view of the regulation of the oligodendroglial lineage by protein growth factors and cell-cell contact; and b) to learn how to enhance oligodendroglial regeneration following multiple sclerosis and other demyelinating diseases. Studies relevant to these goals during the present granting period have shown: a) that germinal matrix oligodendroglial progenitor cells present in neonatal rat forebrain can fully regenerate the oligodendroglial lineage in cultures immunologically stripped of oligodendroglia and """"""""O-2A"""""""" oligodendroglial precursors if provided with platelet-derived growth factor (PDGF); b) that mature oligodendroglia can be induced to proliferate by treatment with a brain membrane-associated protein (""""""""brain membrane-associated oligodendroglial growth factor"""""""", BMOGF) that is distinct from other known oligodendroglial growth factors; and c) that mature oligodendroglia can be induced to """"""""dedifferentiate"""""""" to 0-2A cells when treated with basic fibroblast growth factor (basic FGF).
The specific aims of this competitive renewal are to: 1) clone and sequence BMOGF, determine its distribution and developmental expression, and investigate the mechanism by which it inhibits expression by oligodendroglia of myelin proteins; 2) determine the trophic effects of basic fibroblast growth factor (basic FGF) and platelet-derived growth factor (PDGF) on germinal matrix oligodendroglial progenitor cells; 3) determine the developmental pattern of expression by the oligodendroglial lineage of genes encoding receptors for basic FGF, PDGF, and other members of the protein tyrosine kinase family of plasma membrane growth factor receptors; and 4) examine in more detail the effects of basic FGF and BMOGF on mature oligodendroglia.
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