We will continue our current research on several aspects of CNS glial cells. 1) Glial cell lineages in the brains of developing rats are being followed in vivo and in vitro using antibodies which identify glia in different developmental stages. We propose to investigate spinal cord gliogenesis to test the hypothesis that immature, radial glia can give rise to both astrocytes and oligodendrocytes. We will continue an ultrastructural examination of immature cells labeled with an antibody to GD3 ganglioside, a membrane component of immature neuroectodermal cells and developing glia, focusing particularly on gliogenesis in gray matter regions. The nature of the residual, GD3 - positive cells that are found in the subventricular regions of the adult mammalian CNS will also be investigated by examining the fate of these cells in tissue culture. 2)-The metabolic regulation of glial fibrillary acidic protein (GFAP), an intermediate filament protein of astrocytes which increases in pathological conditions, will be examined. These studies involve determining levels of GFAP translation and protein under several conditions which we have found to modulate GFAP mRNA cells in astrocytes and astrocytoma cells in culture. 3) Further studies characterizing a protein component of Rosenthal fibers will be performed. These are inclusions that accumulate in astrocytes in Alexander's disease, a degenerative disorder of childhood. Initial studies have determined the present of ubiquitin, a small protein involved in proteolytic processing. Proposed work includes a full sequence analysis, a determination of the cellular specificity of this protein, and studies to explore how astrocytes may regulate the levels of this protein.
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