The objective of this research is to understand the signaling mechanisms that cells use to migrate and that axon growth cones use to home to their synaptic targets. To elucidate these mechanisms and their underlying molecular components, we are identifying and characterizing axon guidance and cell migration mutants in a model animal, C. elegans. We and others have shown that C. elegans uses many of the same molecular mechanisms (e.g., UNC-6/netrin signaling) used to guide cell and axon migrations in the mammalian spinal cord and C.N.S. These mutants allow us to identify novel components of migration mechanisms used by cells and axons, and fit them into a molecular pathway whose functional output we can monitor in vivo. We have discovered a novel TGF-beta signaling pathways that guides cell and axon migrations in C. elegans and have identified additional mutants that should allow us to reveal how this pathway and the UNC-6/netrin signaling pathway function during the development of the nervous system as well as other organ systems. An understanding of these pathways should help identify homologous pathways in humans, and provide potential targets for therapeutic interventions aimed at regenerating neurons or preventing spread of metastatic cancer cells.
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