Patterning dendritic branches with environmental and neuronal surface molecules

描述(申请人提供)：树突状乔木采用不同复杂性的不同分支形态，这是特定神经元类型的特征。树突枝的组织对神经元的连通性和功能至关重要。尽管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尚不清楚。特别是，我们对促进和引导有图案的树突分支的膜分子缺乏了解。这项拨款的总体目标是确定新的分子配体和受体，以产生线虫伤害性PVD神经元复杂而有序的树突分支。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。继我们最近发现的对PVD树突形态发生至关重要的跨膜富含亮氨酸的重复分子DMA-1之后，在特定的目标1中，我们将通过进一步鉴定其功能丧失表型、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。在特定的目标2中，我们将探索细胞黏附L1CAM/SAX-7在产生有图案的树突状分支中的作用。我们将研究SAX-7的功能丧失和获得表型，确定其细胞需求，并检查其亚细胞定位。我们还将研究一个 新的跨膜蛋白W01F3.1，我们从一个正向遗传筛选中分离到。在特定的AIM 3中，我们将使用遗传和生化手段测试DMA-1、SAX-7和W01F3.1是否形成三方配体-受体复合体，从而形成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.