Cell Interaction-Dependent Neural Development

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The long-term objectives of this research plan are to define the mechanisms of heterotypic cell-cell interactions which regulate the normal development and maturation of embryonic neural cells. Cell differentiation and maturation in neural tissues is a plastic process and subject to change in response to microenviromental cues. Hence, inborn developmental errors likely result when normal cell relations are disturbed by external stimuli or genetic alterations. Certain aspects of neuroglial cell development have been defined which are dependent on neuronal-glial interactions for normal and timely expression. Specific probes of cell surface components have been defined which interfere with this interaction between heterotypic cells. The cell surface molecules which react with the inhibitory probes will be defined and their role in cell-cell communication investigated. Biochemical and immunochemical analyses will be conducted to define the molecular interactions involved. Defined subcategories of neural cells will be isolated by immunomagnetic separation. The defined cell types will be recombined with other defined populations of cells in vitro under varying controlled conditions and the effects of cell interaction inhibitors determined. Biochemical analysis of communication-dependent gene expression will be measured. Studies will also be conducted in situ to determine whether or not probes which interfere with cell development in vitro will also affect development in the embryo.