GAP JUNCTIONS IN NEURAL DEVELOPMENT

描述（逐字复制摘要）：这些研究的总体目标 是确定缝隙连接在神经祖细胞存活中的作用， 增殖，并致力于神经元和神经胶质谱系，并在 神经元和神经胶质的逐步发育。基本假设 这些研究表明，缝隙连接通讯协调增殖， 和祖细胞亚群的存活和早期协调 血统承诺，以及祖先物种的功能解偶联是 随后对于退出细胞周期和向特异性细胞转化所必需 血统此后，其他连接蛋白的重新表达， 生物物理特性影响细胞功能。祖细胞的发育 可以通过改变细胞微环境来在体外操纵细胞， 促进神经发生或神经胶质发生。拟议的研究将审查 缝隙连接在调节这些群体发育中的功能作用 在体外，并将确定连接蛋白的表达在发育中的大脑， vivo.他们将研究监管差距之间的关系 连接通讯和祖细胞退出细胞周期， 连接蛋白在神经元后代随后成熟中的作用。他们将 定义决定哪种连接蛋白表达的机制， 神经元和缝隙连接通道的表达是否与 生物物理性质改变发育中的神经元的表型。特别 重点将放在研究连接蛋白36，一个主要的神经间隙连接 大脑中的蛋白质。这些研究应该提供深入了解机制 调节神经发育、谱系定型和表型表达， 以及缝隙连接在调节这些过程中的作用。

Description (Abstract reproduced verbatim): The overall goal of these studies is to define the role of gap junctions in neural progenitor cell survival, proliferation, and commitment to neuronal and glial lineages, and in the progressive development of neurons and glia. The basic hypotheses underlying these studies are that gap junctional communication coordinates proliferation and survival of subpopulations of progenitor cells and orchestrates early lineage commitment, and that functional uncoupling of progenitor species is subsequently necessary for exit from cell cycle and commitment to specific lineages. Thereafter re-expression of other connexins with different biophysical properties influences cell function. The development of progenitor cells can be manipulated in vitro by changing the cellular microenvironment to promote neurogenesis or gliogenesis. The proposed studies will examine the functional role of gap junctions in regulating development of these populations in vitro, and will define connexin expression in the developing brain in vivo. They will examine the relationship between the regulation of gap junctional communication and exit of progenitor cells from cell cycle and the role of connexins in the subsequent maturation of neuronal progeny. They will define mechanisms that determine which connexin is expressed by developing neurons and whether the expression of gap junction channels with different biophysical properties alters the phenotype of developing neurons. Particular focus will be placed on the study of connexin 36, a major neuronal gap junction protein in the brain. These studies should provide insight into mechanisms regulating neural development, lineage commitment, and phenotypic expression, and into the role of gap junctions in regulating these processes.