Patterning dendritic branches with environmental and neuronal surface molecules

描述（由申请人提供）：树突状乔木采用不同复杂性的不同分支形态，这是给定神经元类型的特征。树突的组织对于神经元的连接和功能是至关重要的。虽然对神经系统的形状和连通性至关重要，但调节树突形态的机制还不清楚。特别是，我们缺乏对促进和引导模式化树突状分支的膜分子的理解。这项研究的总体目标是鉴定新的分子配体和受体，这些配体和受体产生C.优雅我们的假设是，膜分子之间的相互作用引导树突生长和分支的环境。继我们最近发现的跨膜富含亮氨酸的重复分子DMA-1是PVD树突状形态发生所必需的，在具体的目标1中，我们将通过进一步表征其功能丧失表型，测试其充分性并寻找其相互作用伙伴来进一步了解DMA-1的功能。在具体目标2中，我们将探索细胞粘附L1 CAM/SAX-7在产生图案化树突状分支中的功能。我们将研究sax-7的功能丧失和获得表型，确定其细胞需求并研究其亚细胞定位。我们还将研究 新的跨膜蛋白W01F3.1，我们从正向遗传筛选中分离。在特定的aim 3中，我们将测试DMA-1，SAX-7和W01F3.1是否形成三重配体-受体复合物，该复合物使用遗传和生物化学手段来形成PVD树突。

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.