Calcium signaling in neuronal differentiation

神经元分化中的钙信号传导

基本信息

批准号：
6924515
负责人：
Lori Redmond
金额：
$ 25.98万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-20 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6924515
关键词：
biological signal transduction cAMP response element binding protein calcium flux calmodulin cell differentiation cell morphology confocal scanning microscopy dendrites developmental neurobiology gene mutation gene targeting genetic regulation genetic transcription genetically modified animals green fluorescent proteins laboratory mouse mitogen activated protein kinase neurogenesis neurons pyramidal cells tissue /cell culture

biological signal transduction cAMP response element binding protein calcium flux calmodulin cell differentiation cell morphology confocal scanning microscopy dendrites developmental neurobiology gene mutation gene targeting genetic regulation genetic transcription genetically modified animals green fluorescent proteins laboratory mouse mitogen activated protein kinase neurogenesis neurons pyramidal cells tissue /cell culture

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项目摘要

DESCRIPTION (provided by applicant): The long term goal of my research program is to understand cellular and molecular mechanisms regulating neuronal development and differentiation, specifically neuronal connectivity. Patterning and connectivity of neurons in vivo is profoundly influenced by neuronal activity. Yet, the molecular mechanisms by which activity controls neuronal structure remain unclear. The overall goals of this research project are to identify and ascertain the contribution of activity-driven molecular signals to neuronal development and specifically to dendrite morphology. We have previously shown that activation of intracellular calcium signaling pathways increases global dendritic complexity in a transcription dependent manner similar to that reported in learning and memory. Activity induced dendritic complexity is mediated by the sequential activation of CaM kinase IV and CREB/CBP-mediated signaling. The specific aims of this project are: (i) to determine the mechanisms by which activity is transduced into dendritic branching and process initiation, (ii) to ascertain the requirement for CaMKIV- and CREB-mediated signaling in dendritic development and gene transcriptional control of dendritic elaboration, and (iii) to ascertain in vivo dendrite development in the absence of CaMKIV or CREB signaling. Failure to develop normal neuronal morphology and establish appropriate connections within the central nervous system is believed to be a central feature of mental retardation. Understanding the molecular events contributing to neuronal morphology and dendrite development will help us understand how the brain develops, what can go wrong in developmental disorders, and identify potential targets for therapeutic intervention.

描述（由申请人提供）：我的研究计划的长期目标是了解调节神经元发育和分化的细胞和分子机制，特别是神经元连接。体内神经元的图案和连通性受神经元活性的深刻影响。然而，活性控制神经元结构的分子机制尚不清楚。该研究项目的总体目标是确定和确定活动驱动的分子信号对神经元发展，特别是对树突形态的贡献。我们先前已经表明，细胞内钙信号通路的激活以类似于学习和记忆中报告的转录方式增加了全局树突复杂性。活性引起的树突状复杂性是由CAM激酶IV和CREB/CBP介导的信号传导的顺序激活介导的。 The specific aims of this project are: (i) to determine the mechanisms by which activity is transduced into dendritic branching and process initiation, (ii) to ascertain the requirement for CaMKIV- and CREB-mediated signaling in dendritic development and gene transcriptional control of dendritic elaboration, and (iii) to ascertain in vivo dendrite development in the absence of CaMKIV or CREB signaling.未能发展正常的神经元形态并在中枢神经系统中建立适当的联系被认为是智力低下的核心特征。了解有助于神经元形态和树突发育的分子事件将有助于我们了解大脑如何发展，发育障碍中可能出问题的事物，并确定治疗性干预的潜在靶标。