Patterning dendritic branches with environmental and neuronal surface molecules

描述（由申请人提供）：树突乔木具有不同的分支形态，具有不同的复杂性，这是给定神经元类型的特征。树突乔木的组织是神经元连通性和功能的基础。尽管对神经系统的形状和连通性至关重要，但调控树突形态的机制尚不清楚。特别是，我们对促进和引导树突分支的膜分子的理解是缺乏的。这项资助的总体目标是鉴定新的分子配体和受体，这些配体和受体在秀丽隐杆线虫中产生复杂而有序的伤害性PVD神经元树突分支。我们的假设是膜分子之间的相互作用引导树突在其环境中生长和分支。在我们最近发现的富含亮氨酸的跨膜重复分子DMA-1对PVD树突形态发生至关重要的基础上，在特定目标1中，我们将通过进一步表征其功能缺失表型、测试其充分性和寻找其相互作用伙伴来进一步了解DMA-1的功能。在具体的目标2中，我们将探索细胞粘附L1CAM/SAX-7在树突状分支生成中的功能。我们将检查sax-7的功能丧失和功能获得表型，确定其细胞需求并检查其亚细胞定位。我们也会研究a的函数

DESCRIPTION (provided by applicant): Dendritic arbors adopt diverse, branched morphologies of varying complexity that are characteristic for a given neuron type. The organization of the dendritic arbors is fundamental to the connectivity and function of a neuron. Although critical to the shape and connectivity of the nervous system, the mechanisms that regulate dendrite morphology are not well understood. In particular, our understandings of membrane molecules that promote and guide patterned dendritic branches are lacking. The overall goal of this grant is to identify novel molecule ligands and receptors that generate the complex and orderly dendrite branches of the nociceptive PVD neurons in C. elegans. Our hypothesis is that interactions between membrane molecules guide dendritic growth and branching in its environment. Following up on our recent discovery of a transmembrane leucine-rich repeat molecule DMA-1 that is essential for PVD dendritic morphogenesis, in specific aim 1, we will further understand the function of DMA-1 by further characterizing its loss-of-function phenotypes, testing its sufficiency and searching for its interaction partners. In specific aim 2, we will explore the function of cell adhesion L1CAM/SAX-7 in generating patterned dendritic branches. We will examine the loss- and gain-of-function phenotype of sax-7, determine its cellular requirement and examine its subcellular localization. We will also study the function of a novel transmembrane protein W01F3.1, which we isolated from a forward genetic screen. In specific aim3, we will test if DMA-1, SAX-7 and W01F3.1 form a tripartite ligand-receptor complex that pattern PVD dendrite using genetic and biochemical means.