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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS017125-10
Application #
3397364
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1989-07-01
Project End
1995-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
10
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Jang, Eun Sook; Goldman, James E (2011) Pax6 expression is sufficient to induce a neurogenic fate in glial progenitors of the neonatal subventricular zone. PLoS One 6:e20894
Assanah, M C; Bruce, J N; Suzuki, S O et al. (2009) PDGF stimulates the massive expansion of glial progenitors in the neonatal forebrain. Glia 57:1835-47
Lin, Grace; Mela, Angeliki; Guilfoyle, Eileen M et al. (2009) Neonatal and adult O4(+) oligodendrocyte lineage cells display different growth factor responses and different gene expression patterns. J Neurosci Res 87:3390-402
Lin, Grace; Goldman, James E (2009) An FGF-responsive astrocyte precursor isolated from the neonatal forebrain. Glia 57:592-603
Cayre, Myriam; Canoll, Peter; Goldman, James E (2009) Cell migration in the normal and pathological postnatal mammalian brain. Prog Neurobiol 88:41-63
Mela, Angeliki; Goldman, James E (2009) The tetraspanin KAI1/CD82 is expressed by late-lineage oligodendrocyte precursors and may function to restrict precursor migration and promote oligodendrocyte differentiation and myelination. J Neurosci 29:11172-81
Ivkovic, Sanja; Canoll, Peter; Goldman, James E (2008) Constitutive EGFR signaling in oligodendrocyte progenitors leads to diffuse hyperplasia in postnatal white matter. J Neurosci 28:914-22
Canoll, Peter; Goldman, James E (2008) The interface between glial progenitors and gliomas. Acta Neuropathol 116:465-77
Milosevic, Ana; Noctor, Stephen C; Martinez-Cerdeno, Veronica et al. (2008) Progenitors from the postnatal forebrain subventricular zone differentiate into cerebellar-like interneurons and cerebellar-specific astrocytes upon transplantation. Mol Cell Neurosci 39:324-34
Ventura, Rachel E; Goldman, James E (2007) Dorsal radial glia generate olfactory bulb interneurons in the postnatal murine brain. J Neurosci 27:4297-302

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