Neuron Migration in C. elegans

描述(申请人提供)：神经元胞体和生长锥 迁徙塑造了神经系统的整体模式和连接性。这个 这项拟议研究的目标是调查 控制神经元的迁移。了解这些基本机制可能会导致 对如何修复受损的神经系统的见解。应用程序 有四个具体目标。 以确定EGL-20WNT是否作为HSN的指导线索。这个 HSN运动神经元的迁移需要Wnt同源基因EGL-20，并且 初步实验表明，EGL-20作为一种指导信号，一种新颖的 WNT的活动。确定EGL-20是否将HSN引导到他们的 目的地，EGL-20将被错误表达。EGL-20WNT中的下游组件 将被确定他们是否在HSN行动。 1.研究HSN迁移过程中CAM-1、ROR激酶对EGL-20的拮抗作用。 EGL-20和CaM-1突变之间的遗传相互作用表明这些 HSN迁移过程中基因相互拮抗。CAM-1可以改变 通过与EGL-20直接结合来分布EGL-20。或者，CAM-1 可以编码单独的信号通路的一个组成部分，该信号通路可以拮抗 EGL-20。一系列的基因和分子实验被提议用来 区分这些假设。 2.进一步研究Abelson癌基因abl-1在细胞迁移中的作用 并确定作用于ABL-1途径的基因。Abelson癌基因扮演着一种 在其他生物的生长锥迁移中发挥核心作用。在线虫中， ABL-1和CAM-1一样，拮抗EGL-20在HSN迁移过程中的活性。 建议进行实验以确定ABL-1功能的哪些部分在 迁移，以确定ABL-1的功能位置，并识别 行动与ABL-1。 3.明确VAB-8/UNC-51相互作用在细胞和生长锥中的作用 迁徙。VAB-8与保守的丝氨酸/苏氨酸相互作用 激酶UNC-51。初步实验还表明，UNC-51可以 磷酸化VAB-8L。VAB-8/UNC-51的功能意义 将测试相互作用和VAB-8磷酸化的作用。

DESCRIPTION (provided by applicant): Neuronal cell body and growth cone migrations shape the overall pattern and connectivity of nervous systems. The objective of the proposed research is to investigate the mechanisms that control neuronal migrations. Understanding these basic mechanisms could lead to insights into how damaged nervous systems might be repaired. The application has four specific aims. To determine whether EGL-20 Wnt acts as a guidance cue for the HSN. The migrations of the HSN motor neuron require the Wnt homolog EGL-20, and preliminary experiments suggest that EGL-20 acts as a guidance cue, a novel activity for a Wnt. To determine whether EGL-20 guides the HSNs to their destinations, EGL-20 will be misexpressed. Downstream components in EGL-20 Wnt will be identified to determine whether they act in the HSN. 1. To determine how the CAM-1 Ror kinase antagonizes EGL-20 in HSN migration. Genetic interactions between the egl-20 and cam-1 mutations indicate that these genes antagonize each other in HSN migration. CAM-1 could alter the distribution of EGL-20 by directly binding to EGL-20. Alternatively, CAM-1 could encode a component of a separate signaling pathway that antagonizes EGL-20. A series of genetic and molecular experiments are proposed to distinguish between these hypotheses. 2. To further characterize the role of Abelson oncogene ABL-1 in cell migration and identify genes that act in the ABL-1 pathway. The Abelson oncogene plays a central role in the growth cone migrations of other organisms. In C. elegans, ABL-1, like CAM-1, antagonizes the activity of EGL-20 in HSN migration. Experiments are proposed to determine which portions of ABL-1 function in migration, to determine where ABL-1 functions, and to identify molecules that act with ABL-1. 3. To define the roles of VAB-8/UNC-51 interactions in cell and growth cone migrations. VAB-8 interacts physically with the conserved serine/threonine kinase UNC-51. Preliminary experiments also suggest that UNC-51 can phosphorylate VAB-8L. The functional significance of the VAB-8/UNC-51 interactions and the role of VAB-8 phosphorylation will be tested.