Signaling Pathways That Differentiate Dendrite and Axon Development

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，人们知之甚少。这个 这项应用的长期目标是定义如何在治疗期间实现神经元的区隔 神经回路的发展以及在这一过程中的缺陷如何导致神经和 精神疾病。这个应用程序的目标是描绘信号通路 分离树突和轴突的发育。最近的遗传学研究表明，成纤维细胞 生长因子受体不同地控制树突和轴突的发育。中环 这一应用的假设是，成纤维细胞生长因子受体激活不同的信号通路，以 区别控制树突和轴突的发育。我们将通过追求三个方面来检验这一假设 具体目的：1)确定成纤维细胞生长因子受体控制树突状细胞特异性的信号通路 2)确定成纤维细胞生长因子受体是否通过多种途径调节轴突发育 不同于树突的发育；3)识别执行树突的效应分子- 由Dar1介导的特定发育。这种方法是创新的，因为它利用了 研究树突发育差异的遗传学和新的分子分析 和体内的轴突。这项拟议的研究具有重要意义，因为它有望推动知识的进步 树突和轴突不同发育的信号机制。那 需要知识来制定战略，以便优先或具体地操纵 树突状或轴突在疾病条件和动物模型中的发育以询问其功能 神经系统的一部分。

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 have suggested 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) Identify the effector molecules that execute the dendrite- specific development mediated by Dar1. The approach is innovative because it takes advantage of genetic and novel molecular analyses to investigate the developmental differences between dendrites and axons in vivo. 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.