The long term goal of the proposed reserach is to determine the role of gangliosides in neuritogenesis, in order to better understand the basic mechanisms of neuronal development and regeneration. The immediate goals are to: 1) define the role of gangliosides in Nerve Growth Factor (NGF)-mediated neuritogenesis; 2) to investigate the role of gangliosides in NGF-independent trophic interactions and 3) to determine the cytoskeletal basis of ganglioside-enhanced neuronal differentiation. In the remaining twenty-one months of this grant we will: 1) explore the neuritogenic capacities of four major gangliosides (GM1, GD1a, GD1b and GT1b) biochemically and morphologically on primary and established neuronal models in vitro; 2) determine the action of monoclonal antibodies, directed against specific gangliosides, on neuronal differentiation; 3) examine the cytoskeletal basis of ganglioside-mediated neuritogenesis by employing agents which disrupt or stabilize structural components of the neuron and 4) probe the ganglioside distribution and fluidity of neuronal membranes. We will continue studies aimed to examine the relationship between ganglioside-mediated changes in neuronal surface topography, metabolic activity and neuronal elongation. Histochemical and morphological probes, including lectins, toxins, taxol, colcemid and cytochalasin D will be employed in these ongoing studies. We hope that information gained from these in vitro studies will elucidate basic mechanisms essential to neuronal differentiation.
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