Mechanisms that differentiate dendrite development from axon development

神经元的树突和轴突如何发展成不同的形态--这是组装的基础 神经回路--人们对此知之甚少。了解树突和轴突的区别机制 因此，发展是发展神经科学的一个重要目标。以下是几种监管机制 致力于体内树突特异性或轴突特异性生长的研究已经通过利用 果蝇系统的。此外，抑制树突状细胞生长但促进轴突生长的分子途径 同一神经元内的生长(即，双峰机制)位于这些专用神经元的上游 机械装置。双峰调节为植物形态多样性的产生提供了独特的机制 神经元，并与设计有效的策略以再生受伤或患病的神经有关 系统。这项研究的长期目标是定义神经元如何发育成不同的亚细胞部分。 以及这一过程中的缺陷如何导致人类疾病。拟议研究的目的是揭示 树突和轴突生长双峰调控的分子和细胞机制。最近的研究表明 研究表明，进化上保守的双亮氨酸拉链激酶/Wallenda(DLK/WND)通路是一条双峰通路 树突状细胞和轴突生长的调节者，这一途径调节转录水平 因子(KNOT)和细胞黏附分子(DSCAM)分别控制树突状和轴突生长。 初步研究提出了一个新的概念：通过RNA结合蛋白进行翻译调控 树突状和轴突生长的双峰控制核心。下面的模型，集成了特定的分子 以及它们的空间位置调节双峰控制，将被测试：DLK/WND通路调节 两种不同的RNA结合蛋白控制PABP依赖的轴突终末DSCAM翻译的启动 对于轴突生长和结节在胞体中的表达分别为树突状生长。这款车型将是 通过鉴定(A)DLK/WND通路调节轴突终末的分子机制进行测试 发育和树突分支发育以及(B)DLK/WND的亚细胞位置 通路调节下游因子，指导树突和轴突的差异生长。建议数 研究具有创新性，因为它提出了树枝晶差异发展的新概念和 并采用了几种非常适合这一研究领域的创新技术。这项研究是 意义重大，因为它有望为树突和轴突之间的协调提供关键的见解 发展，确定翻译控制在树枝晶和树枝晶的差异发育中所起的关键作用 轴突，发现DLK/WND通路在神经元中发挥作用的新机制，并提供见解 神经发育障碍的发病机制。

How a neuron’s dendrites and axons develop into distinct morphology—which is fundamental to the assembly of neural circuits—is poorly understood. Understanding the mechanisms that differentiate dendrite and axon development, therefore, is a vital goal in developmental neuroscience. Several regulatory mechanisms that are dedicated to either dendrite-specific or axon-specific growth in vivo have been identified by taking advantage of a Drosophila system. In addition, a molecular pathway that suppresses dendritic growth but promotes axonal growth within the same neuron (i.e., a bimodal mechanism) has been located upstream of these dedicated mechanisms. The bimodal regulation provides a unique mechanism for generating morphological diversity in neurons, and is relevant for the design of effective strategies to regenerate an injured or diseased nervous system. The long-term goal of this research is to define how a neuron develops into distinct subcellular parts and how defects in this process lead to human disease. The objective of the proposed studies is to uncover the molecular and cellular mechanisms of bimodal controls of dendritic and axonal growth. Recent studies have shown that the evolutionarily conserved dual leucine zipper kinase/Wallenda (DLK/Wnd) pathway is a bimodal regulator of dendritic and axonal growth, and that this pathway regulates the expression levels of a transcription factor (Knot) and a cell adhesion molecule (Dscam) to control dendritic and axonal growth, respectively. Preliminary studies suggest a novel concept: Translational regulation through RNA-binding proteins is at the core of bimodal control of dendritic and axonal growth. The following model, which integrates specific molecules and regulations with their spatial locations for bimodal control, will be tested: The DLK/Wnd pathway regulates two distinct RNA-binding proteins to control PABP-dependent initiation of Dscam translation in axon terminals for axonal growth and Knot expression in the cell body for dendritic growth, respectively. This model will be tested by identifying (a) the molecular mechanism by which the DLK/Wnd pathway regulates axon-terminal development and dendritic branch development and (b) the subcellular locations at which the DLK/Wnd pathway regulates downstream factors to instruct the differential growth of dendrites and axons. The proposed research is innovative because it proposes a novel concept in the differential development of dendrites and axons and employs several innovative techniques that are well suited for this line of research. This research is significant because it is expected to offer key insights into the coordination between dendritic and axonal development, identify a critical role translational control plays in the differential development of dendrites and axons, discover novel mechanisms by which the DLK/Wnd pathway functions in neurons, and provide insights into the pathogenesis of neurodevelopmental disorders.