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. Recently, a monoclonal antibody raised against the B49 cell line has identified a cell surface ganglioside antigen specifically found on germinal cells within the CNS. This antigen, designated as Dl.l, has been found on the surfaces of neuroepithelial cells, the stem cells of the CNS but it is not detected on the differentiated progeny of these cells. The derivation of the anti-Dl.l antibody and the identification of the antigen provide an opportunity to analyze the early development of the CNS at the cellular and biochemical level.
The specific aims of the proposal are to 1) define the chemical structure of the Dl.l ganglioside antigen and identify the biochemical mechanisms responsible for its expression on germinal cells and for its subsequent loss or disappearance during neuronal and glial differentiation, 2) map the complete tissue and cellular distribution of the antigen during embryogenesis to determine whether the antigen may be a marker for stem cells that can give rise to some but not all neuroectodermally derived cell types, 3) test the functional role of the Dl.l ganglioside incell-cell and cell-substrate adhesion and in growth control, 4) analyze the expression of cell surface and intracellular markers characteristic of mature neurons and glial cells by Dl.l positive germinal cells and 5) isolate CNS germinal cells by fluorescence activated cell sorting and analyze their capacity to differentite in vitro. In addition, isolated terminal cells will be microinjected into post-natal and adult brain to determine whether germinal cells differentiate according to their origin or according to their new environment. The proposed studies should lead to an understanding of the cellular basis of neuronal and glial differetiation and to an evaluation of the functional role of the Dl.l ganlioside in the processes of development.
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