Growth & Dev of the Nervous System: Molecular Mechanisms

生长

• 批准号: 6750686
• 负责人: IRA B BLACK
• 金额: $ 140.45万
• 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 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6750686
• 关键词: developmental neurobiology; neurotrophic factors

DESCRIPTION (provided by applicant): The central objective of this program project is to define integrative principles governing the diverse processes of brain development and plasticity. We hypothesize that reciprocal stem cell differentiation, and neuron-neuron and neuron-Glial-neuron interactions, mediated by a limited set of inter- and intra-cellular signals, coordinate gene expression and seemingly unrelated developmental events. Moreover, specific genes, such as Rab3A, regulate trophin-induced synaptic plasticity. Specifically: a) trophic factors, including the diffusible neurotrophin gene family members, b) growth (mitogenic) factors, including bFGF and IGF-1, mediated by cyclins, CDKs and CKIs, c) membrane-bound cellular labels of the Eph gene family, d) neurotransmitters and the hormone, estradiol and e) the newly discovered intracellular trophin transduction molecule ARMS, working combinatorially, synchronize the developmental sequence. These molecular signals coordinate stem cell commitment and differentiation, neuronal mitosis, selective survival, axonal pathfinding, topographic projection, synaptogenesis and synaptic plasticity. We will employ multidisciplinary molecular genetic, transcriptional, biochemical and morphologic approaches at the population and single cell levels to study development and plasticity in vivo and in culture. We plan to define a) epigenetic regulation of stem cell and precursor mitosis and differentiation, b) the roles of bFGF and IGF-1 in cortical development, c) the role(s) of ARMS in mediating p75 and trk neurotrophin receptor actions in development and plasticity, d) the actions of Eph ligands and receptors in axon defasciculation and synaptogenesis in targets, e) trophic regulation of genes at the single cell level regulating synaptic plasticity and synaptogenesis, and f) the role of astrocyte-neuron interactions in brain development.

描述（由申请人提供）：该计划项目的核心目的是定义统治大脑发育和可塑性过程的综合原则。我们假设相互的干细胞分化以及神经元 - 神经元和神经元 - 神经元的相互作用，这是由有限的细胞间和细胞内信号，坐标基因表达以及看似无关的发育事件介导的。此外，特定的基因（例如RAB3A）调节了滋养蛋白诱导的突触可塑性。具体而言：a）营养因素，包括可扩散性神经营养蛋白基因家族成员，b）生长（有丝分裂）因素，包括BFGF和IGF-1，由细胞周期蛋白，CDKS和CKIS介导转导分子臂，合并工作，同步发育序列。 这些分子信号坐标了干细胞的承诺和分化，神经元有丝分裂，选择性生存，轴突探路，地形投影，突触发生和突触可塑性。我们将在人群和单细胞水平上采用多学科分子遗传，转录，生化和形态学方法来研究体内和培养中的发展和可塑性。我们计划定义a）干细胞和前旋转有丝分裂和分化的表观遗传调节，b）B）BFGFF和IGF-1在皮质发育中的作用，c）臂在介导P75和TRK神经营养蛋白受体作用中的作用（S）在发育和可塑性中的作用，D）调节基因在调节突触可塑性和突触发生的单细胞水平上，f）星形胶质细胞 - 神经元相互作用在脑发育中的作用。