Signaling Pathways That Differentiate Dendrite and Axon Development

描述（申请人提供）：神经系统的信息处理依赖于树突和轴突的分离。然而，关于树突和轴突如何发育成不同的隔室，我们知之甚少。该应用程序的长期目标是确定神经回路发育过程中神经元区隔化是如何实现的，以及该过程中的缺陷是如何导致神经和精神疾病的。本应用程序的目的是描述分离树突和轴突发育的信号通路。最近对果蝇的遗传研究表明，成纤维细胞生长因子（FGF）受体对树突和轴突的发育具有不同的控制作用。该应用的中心假设是FGF受体激活不同的信号通路，以不同的方式控制树突和轴突的发育。我们将通过追求三个特定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受体在哺乳动物神经元树突和轴突差异发育中的作用是否保守。该方法具有创新性，因为它利用遗传分析来研究体内树突和轴突之间的发育差异，并结合果蝇和哺乳动物系统来研究进化保守的机制。这项研究具有重要意义，因为它有望促进对树突和轴突差异发育的信号机制的了解。需要这些知识来制定策略，以便在疾病条件和动物模型中对树突或轴突的发育进行优先或特定的操作，以询问神经系统的功能。

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.