GAP JUNCTIONS IN NEURAL DEVELOPMENT

描述(摘要逐字转载)：这些研究的总体目标 确定缝隙连接在神经前体细胞存活中的作用， 增殖和对神经元和神经胶质细胞谱系的承诺，以及在 神经元和神经胶质细胞的渐进性发育。潜在的基本假设 这些研究表明，缝隙连接通讯协调细胞增殖。 以及早期祖细胞和编曲细胞亚群的存活 血统承诺，祖先物种的功能分离是 随后有必要退出细胞周期并致力于特定 血统。此后，其他连接蛋白的重新表达与不同的 生物物理特性影响细胞功能。祖细胞的发展 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形成。建议的研究将检视 缝隙连接在调节这些群体发育中的功能作用 ，并将确定在发育中的大脑中连接蛋白的表达 活着。他们将研究GAP的监管与 祖细胞在细胞周期中的连接通讯和退出 连接蛋白在神经元后代随后成熟中的作用。他们会 定义确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具有不同 生物物理特性改变了发育中的神经元的表型。特例 重点将放在连接蛋白36的研究上，这是一种主要的神经元缝隙连接 大脑中的蛋白质。这些研究应该提供对机制的洞察 调节神经发育、血统承诺和表型表达， 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.