Signaling Pathways That Differentiate Dendrite and Axon Development

区分树突和轴突发育的信号通路

• 批准号: 8106098
• 负责人: BING YE
• 金额: $ 38.42万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-05 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8106098
• 关键词: Animal Model; Axon; Defect; Dendrites; Development; Disease; Drosophila genus; Event; Fibroblast Growth Factor; Fibroblast Growth Factor Receptors; Genetic; Genetic Screening; Goals; Growth; Hippocampus (Brain); Homologous Gene; Knowledge; Laboratories; Lead; Link; MAPK8 gene; Mediating; Membrane; Mental disorders; Mitogen-Activated Protein Kinases; Molecular; Nervous System Physiology; Nervous system structure; Neurons; Neurosciences; Pathway interactions; Phenotype; Process; Rattus; Regulation; Research; Research Design; Role; Signal Pathway; Signal Transduction; System; Testing; Therapeutic; Work; axon growth; base; experience; genetic analysis; human disease; in vivo; information processing; innovation; knock-down; nervous system disorder; neural circuit; novel; public health relevance; receptor; transcription factor

DESCRIPTION (provided by applicant): Information processing in the nervous system relies on the separation of dendrites and axons. However, little is known about how dendrites and axons develop into distinct compartments. The long-term goal of this application is to define how neuronal compartmentalization is achieved during the development of neural circuits and how defects in that process lead to neurological and psychiatric diseases. The objective of this application is to delineate the signaling pathways that separate dendrite and axon development. Recent genetic studies on Drosophila have demonstrated that the fibroblast growth factor (FGF) receptors differentially control dendrite and axon development. The central hypothesis of this application is that the FGF receptors activate distinct signaling pathways to differentially control dendrite and axon development. We will test this hypothesis by pursuing three specific aims: 1) ) Identify the signaling pathway through which FGF receptors control dendrite-specific development; 2) Determine whether FGF receptors regulate axon development through pathways different from dendrite development; 3) Determine whether the roles of FGF receptors in the differential development of dendrites and axons are conserved in mammalian neurons. The approach is innovative because it takes advantage of genetic analysis to investigate the developmental differences between dendrites and axons in vivo and combines both Drosophila and mammalian systems to study evolutionarily conserved mechanisms. The proposed research is significant because it is expected to advance knowledge of the signaling mechanisms underlying the differential development of dendrites and axons. That knowledge is needed to develop strategies that will allow preferential or specific manipulations of dendrite or axon development in disease conditions and in animal models to interrogate the functions of the nervous system. PUBLIC HEALTH RELEVANCE: How the information-receiving (dendrites) and -sending (axons) parts of neurons form is poorly understood. This knowledge is important because many neurological and psychiatric diseases involve defects in these two parts of neurons. The proposed research will provide the knowledge needed to develop therapeutic strategies having subcellular precision to correct defective dendrites and axons in human diseases.

描述（由申请人提供）：神经系统中的信息处理依赖于树突和轴突的分离。然而，很少有人知道树突和轴突如何发展成不同的隔间。该应用程序的长期目标是确定神经元区室化在神经回路的发展过程中是如何实现的，以及该过程中的缺陷如何导致神经和精神疾病。本申请的目的是描绘分离树突和轴突发育的信号通路。最近对果蝇的遗传学研究表明，成纤维细胞生长因子（FGF）受体差异控制树突和轴突的发育。本申请的中心假设是FGF受体激活不同的信号传导途径以差异地控制树突和轴突发育。我们将通过追求三个具体目标来验证这一假设：1））确定FGF受体控制树突特异性发育的信号通路; 2）确定FGF受体是否通过不同于树突发育的途径调节轴突发育; 3）确定FGF受体在树突和轴突差异发育中的作用是否在哺乳动物神经元中是保守的。这种方法是创新的，因为它利用遗传分析来研究树突和轴突在体内的发育差异，并结合果蝇和哺乳动物系统来研究进化上保守的机制。这项研究意义重大，因为它有望推动树突和轴突差异发育的信号机制的知识。需要这些知识来开发策略，以允许在疾病条件下和动物模型中优先或特异性操纵树突或轴突发育，以询问神经系统的功能。 公共卫生相关性：人们对神经元的信息接收（树突）和信息发送（轴突）部分是如何形成的知之甚少。这一知识很重要，因为许多神经和精神疾病都涉及这两部分神经元的缺陷。拟议的研究将提供开发具有亚细胞精度的治疗策略所需的知识，以纠正人类疾病中有缺陷的树突和轴突。