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信号被引导到它们的目标。虽然在这些线索的表征方面取得了很大进展，但对下游信号通路的了解甚少。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。初步证据表明，米格-10可能会调节狭缝（一种排斥性制导信号）下游的信号。将确定两种米格-10亚型的表达模式和功能位点。米格-10可能调节狭缝信号的假设将通过异位表达AVM（一种已知对狭缝的轴突排斥敏感的神经元）中的两种同种异构体来验证。与米格-10相互作用的基因将通过候选基因方法和基因筛选来确定。米格-10基因的产物类似于一个哺乳动物蛋白家族，包括GRB-7、GRB-10和GRB-14。这些蛋白在几种类型的癌症中过度表达，但对它们的功能知之甚少。这个项目的信息将有助于理解神经系统的紊乱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.