Molecular Mechanisms of MIG-10 function in axon guidance

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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.