GROWTH AND DEVELOPMENT OF THE NERVOUS SYSTEM

神经系统的生长和发育

• 批准号: 6387533
• 负责人: IRA B BLACK
• 金额: $ 109.17万
• 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 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6387533
• 关键词: developmental neurobiology; molecular biology; neurotrophic factors

The central objective of this program project is to define integrative principles governing the diverse processes of brain development. We hypothesize that reciprocal neuron-neuron and neuron-glial-neuron interactions, mediated by a limited set of intercellular signals, coordinate seemingly unrelated developmental events. Specifically, (a) trophic factors, including the diffusible neurotrophin gene family members, b) growth (mitogenic) factors, including bFGF, c) membrane-bound, chemorepulsive, cellular labels of the Eph gene family, and d) conventional neurotransmitters working combinatorially, synchronize the developmental sequence. These molecular signals coordinate neuronal mitosis, selective survival, axogenesis, pathfinding, topographic projection and synaptic plasticity. The epigenetic molecular signals mediate and integrate neural activity, trophic and glial coordination of proliferation, selective survival, pathway formation and synaptic function. We will employ multidisciplinary molecular genetic, biochemical and morphologic approaches to study neuronal development in vivo and in culture. We plan to define a) neuroblasts, b) the role of peripheral bFGF in brain neurogenesis, c) the role of the p75 neurotrophin receptor in developmental cell death and survival, d) the role of Eph family ligands and receptors in brain topographic projection, e) trophic regulation of synaptic plasticity and 3) the role of astrocyte-neuron interactions in brain development.

该计划项目的核心目的是定义集成 管理大脑发育过程的多种过程的原则。我们 假设相互神经元神经元和神经元神经元 相互作用，由有限的一组细胞间信号介导， 协调看似无关的发展事件。特别是（a） 营养因子，包括可扩散的神经营养基因家族 成员，b）生长（有丝分裂）因素，包括BFGF，c）膜结合， EPH基因家族的化学螺栓，细胞标签，D） 常规的神经递质合并工作，同步 发展序列。这些分子信号坐标神经元 有丝分裂，选择性生存，轴发生，探路，地形 投影和突触可塑性。表观遗传分子信号 介导并整合神经活动，营养和神经胶质协调 增殖，选择性生存，途径形成和突触 功能。 我们将采用多学科分子遗传，生化和 研究体内神经元发展的形态学方法 文化。我们计划定义a）神经细胞，b）外围BFGF的作用 在脑神经发生中，c）p75神经营养蛋白受体在 发育细胞死亡和生存，d）EPH家族配体的作用 和大脑地形投影中的受体，e）营养调节 突触可塑性和3）星形胶质细胞神经元相互作用在 大脑发育。