Despite a wealth of descriptive and experimental information, little is known about the mechanisms responsible for the early differentiation and development of the mammalian central nervous system. In particular, the developmental lineages that give rise to the diversity of morphological and biochemical phenotypes found in the mature nervous system are poorly understood. Molecules exposed on the surfaces of developing cells may act as markers defining either specific subpopulations of cells or distinct stages in the development of populations of cells. Antibodies that recognize these cell surface markers are potent tools for the analysis of both the cell biology and biochemistry of developing systems. This proposal comprises 2 related projects that utilize existing monoclonal and polyclonal antibodies directed against cell surface molecules of the developing nervous system. In the first project, antibodies against the NG2 antigen (a chondroitin-sulfate proteoglycan) will be used to analyze the plasticity of developing glial cells. The anti-NG2 antibodies recognize a population of smooth protoplasmic astrocytes throughout the brain.
The specific aims are to 1) analyze the phenotypic development of NG2 glia cultured in the absence of neurons 2) assess the effect of nerve-glia contact or nerve secreted material on the phenotypic development of NG2 glia and 3) characterize biochemically histotypic factors that influence the phenotypic development of NG2 glia. The second project focuses on the immunological, and biochemical and functional characterization of cell surface carbohydrate antigens.
The specific aims are 1) analyze the distribution, function and biochemistry of the CHO antigen recognized by a new monoclonal antibody (41.1) 2) elucidate the biochemical mechanisms responsible for the synthesis of an immunologically related family of O-acetylated ganglioside antigens of brain and 3) analyze possible mechanisms of ganglioside enhanced neuritogenesis in the PC12 cell line. These studies will elucidate both the contribution of cell-cell interactions to glial cell differentiation and the functional properties of cell surface glycoconjugates in the developing nervous system.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurology C Study Section (NEUC)
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State University New York Stony Brook
Schools of Arts and Sciences
Stony Brook
United States
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Levine, Joel (2016) The reactions and role of NG2 glia in spinal cord injury. Brain Res 1638:199-208
Dewald, Lisa Evans; Rodriguez, Justin P; Levine, Joel M (2011) The RE1 binding protein REST regulates oligodendrocyte differentiation. J Neurosci 31:3470-83
Nolin, Westley B; Emmetsberger, Jaime; Bukhari, Noreen et al. (2008) tPA-mediated generation of plasmin is catalyzed by the proteoglycan NG2. Glia 56:177-89
Tan, Andrew M; Petruska, Jeffrey C; Mendell, Lorne M et al. (2007) Sensory afferents regenerated into dorsal columns after spinal cord injury remain in a chronic pathophysiological state. Exp Neurol 206:257-68
Morgenstern, Daniel A; Asher, Richard A; Naidu, Murali et al. (2003) Expression and glycanation of the NG2 proteoglycan in developing, adult, and damaged peripheral nerve. Mol Cell Neurosci 24:787-802
Chen, Zhi Jiang; Ughrin, Yvonne; Levine, Joel M (2002) Inhibition of axon growth by oligodendrocyte precursor cells. Mol Cell Neurosci 20:125-39
Martin, S; Levine, A K; Chen, Z J et al. (2001) Deposition of the NG2 proteoglycan at nodes of Ranvier in the peripheral nervous system. J Neurosci 21:8119-28
Diers-Fenger, M; Kirchhoff, F; Kettenmann, H et al. (2001) AN2/NG2 protein-expressing glial progenitor cells in the murine CNS: isolation, differentiation, and association with radial glia. Glia 34:213-28
Ong, W Y; Levine, J M (1999) A light and electron microscopic study of NG2 chondroitin sulfate proteoglycan-positive oligodendrocyte precursor cells in the normal and kainate-lesioned rat hippocampus. Neuroscience 92:83-95
McDonald, J W; Levine, J M; Qu, Y (1998) Multiple classes of the oligodendrocyte lineage are highly vulnerable to excitotoxicity. Neuroreport 9:2757-62

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