Cell Interaction-Dependent Neural Development

这项研究计划的长期目标是确定调控胚胎神经细胞正常发育和成熟的异型细胞-细胞相互作用的机制。神经组织中的细胞分化和成熟是一个可塑性的过程，并受到微环境提示的影响。因此，当正常的细胞关系受到外界刺激或基因改变的干扰时，可能会产生先天发育错误。神经胶质细胞发育的某些方面已经被定义，这些方面依赖于神经元-神经胶质细胞的相互作用来正常和及时地表达。已经定义了干扰异型细胞之间这种相互作用的细胞表面成分的特定探针。将定义与抑制探针反应的细胞表面分子，并研究它们在细胞间通信中的作用。将进行生化和免疫化学分析，以确定所涉及的分子相互作用。确定的神经细胞亚类将通过免疫磁分离来分离。确定的细胞类型将在不同的受控条件下与其他确定的细胞群体在体外重组，并确定细胞相互作用抑制剂的效果。将测量依赖于沟通的基因表达的生化分析。还将进行现场研究，以确定干扰细胞体外发育的探针是否也会影响胚胎的发育。

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.