In previous work, we developed methods for the culture of oligodendroglia, Schwann cells and astroglia, and were the first to demonstrate: 1) a specific mechanism for adhesion of neuroglia to axolemma; 2) that axolemma contact, though stimulating Schwann cell mitosis, markedly inhibits proliferation of cultured astroglia; and 3) that agents which elevate intracellular cyclic adenosine 3', 5'-monophosphate (cyclic AMP) increase synthesis of the myelin lipid galactocerebroside (galC) by both oligodendroglia and Schwann cells. We will now study the process by which mature oligodendroglia are derived from undifferentiated precursor cells. In the rat, these precursor cells, which can develop into either oligodendroglia or glial fibrillary acidic protein (GFAP) rich astroglia, are identifiable by surface binding of a monoclonal antibody, A2B5. We will purify and culture these precursor cells and seek to identify phenotypic markers for them that, unlike A2B5 binding, are related to function and applicable to species other than the rat. We will determine effects on proliferation and differentiation of these cells of activation of cyclic AMP dependent protein kinase, of heparin-binding growth factors, and of growth factors secreted by endothelial cells and astroglia. We have developed a clone of rapidly proliferating, phenotypically stable peripheral neuroglia which synthesizes both a myelin- specific glycoprotein (P/o) and GFAP. This clone will be used to investigate how neuroglial precursor cells are guided to differentiate into either a myelin-forming or a glial filament-rich phenotype.
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