Molecular Mechanisms of MIG-10 function in axon guidance

描述（由申请人提供）：在发育中的神经系统中，轴突通过细胞外引导线索被引导至其靶点。虽然在这些线索的表征方面取得了很大进展，但下游信号传导途径却知之甚少。该项目的目标是确定由mig-10编码的细胞质蛋白的作用，mig-10是SMDD轴突寻路所需的基因。初步的证据表明mig-10可能会调节slit下游的信号传导，这是一种排斥性的引导信号。将确定两种β-10同种型中每一种的表达模式和功能位点。mig-10可以调节狭缝信号传导的假设将通过在AVM中异位表达两种亚型来测试，AVM是一种已知对狭缝轴突排斥敏感的神经元。与mig-10相互作用的基因将通过候选基因方法和遗传筛选来鉴定。mig-10基因的产物类似于哺乳动物蛋白质家族，包括GRB-7、GRB-10和GRB-14。这些蛋白质在几种类型的癌症中过表达，但其功能知之甚少。该项目的信息将有助于了解神经系统疾病以及癌症的分子基础。

DESCRIPTION (provided by applicant): In the developing nervous system, axons are guided to their targets by extracellular guidance cues. While much progress has been made in the characterization of these cues, the downstream signaling pathways are poorly understood. The goal of this project is to determine the role of the cytoplasmic proteins encoded by mig-10, a gene that is required for pathfinding of the SMDD axon. Preliminary evidence suggests that mig-10 might act to modulate signaling downstream of slit, a repulsive guidance cue. The expression pattern and locus of function will be determined for each of two MIG-10 isoforms. The hypothesis that mig-10 may modulate slit signaling will be tested by ectopically expressing both isoforms in the AVM, a neuron that is known to be sensitive to axonal repulsion by slit. Genes that interact with mig-10 will be identified through a candidate gene approach and a genetic screen. The products of the mig-10 gene are similar to a family of mammalian proteins that includes GRB-7, GRB-10, and GRB-14. These proteins are overexpressed in several types of cancers, but their function is poorly understood. Information from this project will be beneficial in understanding disorders of the nervous system as well as the molecular basis of cancer.