GROWTH & DEVELOPMENT OF THE NERVOUS SYSTEM--MOLECULAR

生长

• 批准号: 3097100
• 负责人: IRA B BLACK
• 金额: $ 51.86万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3097100
• 关键词: molecular biology; neurotrophic factors

The central goal of this program project is to elucidate integrative principles regulating brain development by defining sequential ontogenetic processes. We are pursuing the unifying concept that seemingly distinct developmental processes, including neuronal mitosis, aggregation, transmitter and receptor gene expression and trophic interactions with the formation of synaptic circuits are causally interrelated. Although several of these events have been examined in some detail, causal mechanistic relationships among these processes remain unclear. Our studies are now defining critical interactions among these phenomena. We are finding that a number of molecules integrate successive developmental processes through intercellular communication. We will employ multidisciplinary molecular genetic, biochemical, pharmacologic and morphologic approaches to study neuronal development in vivo and in culture. We plan to define a) factors regulating neuronal mitosis, focusing on insulin, a neuronal mitogen recently identified by us; b) regulation of expression of the NGF (nerve growth factor) receptor gene, recently cloned by us; c) mechanisms governing transmitter receptor expression; d) membrane factors governing transmitter phenotypic expression and e) NGF regulation of the formation of brain circuits. Our overall objective is to define molecular mechanistic relations among these apparently diverse developmental processes. Such insights may indicate how seemingly discrete, sequential events causally lead to orderly brain development. This information may define molecular loci where disease processes intervene, leading to abnormal brain development, birth defects and mental retardation.

该计划项目的核心目标是阐明 通过定义来调节大脑发育的综合原则 顺序的个体发生过程。 我们正在追求统一 看似不同的发展过程的概念， 包括神经元有丝分裂，聚集，发射器和受体 基因表达和营养相互作用与形成 突触电路有因果关系。 虽然有几个 这些事件已详细研究，因果关系 这些过程之间的机械关系尚不清楚。 我们的研究现在正在定义这些关键互动 现象。 我们发现许多分子 通过结合连续的发展过程 细胞间沟通。 我们将采用多学科分子遗传，生化， 研究神经元的药理和形态学方法 体内和文化的发展。 我们计划定义a）因素 调节神经元有丝分裂，专注于胰岛素，神经元 我们最近确定的有丝分裂原； b）调节表达的 NGF（神经生长因子）受体基因，最近由 我们; c）控制发射机受体表达的机制； d） 控制发射机表型表达的膜因子 e）NGF调节脑电路的形成。 我们的 总体目标是定义分子机械关系 在这些显然多样化的发展过程中。 这样的 见解可能表明看似离散的顺序事件 有因果导致有序的大脑发育。 此信息 可以定义分子基因座，其中疾病处理干预， 导致脑发育异常，出生缺陷和精神 迟钝。