Molecular Mechanisms of MIG-10 function in axon guidance

描述(申请人提供)：在发育中的神经系统中，轴突被细胞外引导线索引导到它们的靶点。虽然在这些信号的表征方面已经取得了很大的进展，但对下游的信号通路却知之甚少。该项目的目标是确定MiG-10编码的细胞质蛋白的作用，MiG-10是寻找SMDD轴突路径所必需的基因。初步证据表明，米格-10可能会对狭缝下游的信号进行调制，这是一个令人厌恶的引导信号。将确定两种MIG-10亚型的表达模式和功能位点。MiG-10可能调节Sit信号的假设将通过在AVM中异位表达这两种异构体来检验，AVM是一种已知对Sit引起的轴突斥力敏感的神经元。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识别。MiG-10基因的产物与包括GRB-7、GRB-10和GRB-14在内的哺乳动物蛋白质家族相似。这些蛋白质在几种类型的癌症中过度表达，但对它们的功能知之甚少。来自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.