GROWTH AND DEVELOPMENT OF THE NERVOUS SYSTEM

神经系统的生长和发育

• 批准号: 2198822
• 负责人: IRA B BLACK
• 金额: $ 91.57万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 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 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2198822
• 关键词: developmental neurobiology; 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. During the past grant period we have begun to delineate the detailed causal mechanistic relationships among these processes. 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) regulation of peripheral and brain neuron mitosis by epigenetic and genomic factors, studying VIP (vasoactive intestinal peptide), second messenger kinase systems, and the protein Id, a negative regulator of helix-loop-helix DNA binding proteins; b) regulation of expression of the P75NGFR and P140trk product of the proto-oncogene trk, both of which bind NGF, by constructing fusion genes and examining expression in culture and in transgenic mice; c) mechanisms governing synaptic molecular architecture; d) mechanisms through which a fully-purified membrane factor regulates transmitter phenotypic expression and mitosis and e) regulation of the formation of brain circuits by individual members of the neurotrophin gene family. Our overall objective is to define molecular mechanistic relations among apparently diverse developmental processes. 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综合性 通过定义顺序调节大脑发育的原理 个体发生过程。 我们正在追求一个统一的概念 看似不同的发育过程，包括神经元有丝分裂， 聚集，发射器和受体基因表达和营养 与突触电路形成的相互作用是因果关系 相关。 在过去的赠款期间，我们已经开始描述 这些过程之间详细的因果机械关系。 我们的研究现在正在定义这些关键互动 现象。 我们发现许多分子整合 通过细胞间交流进行连续的发展过程。 我们将采用多学科分子遗传，生化， 研究神经元发育的药理和形态学方法 体内和文化。 我们计划定义a）外围的调节 表观遗传和基因组因子和脑神经元有丝分裂，研究VIP （血管活性肠道肽），第二信使激酶系统和 蛋白质ID，螺旋环 - 螺旋DNA结合的负调节剂 蛋白质； b）调节P75NGFR和P140TRK产品的表达 通过构建型NGF的原始癌基因TRK结合了NGF 融合基因并​​检查培养和转基因小鼠中的表达； c）控制突触分子结构的机制； D）机制 完全纯化的膜因子调节发射器 表型表达和有丝分裂以及E）调节的形成 神经营养蛋白基因家族的个体成员的脑回路。 我们的总体目标是定义分子机械关系 显然是多样化的发展过程。 此信息可能定义 疾病过程干预的分子基因座，导致异常 大脑发育，出生缺陷和智力低下。