The long term goal of this research project is to understand how neuronal growth cones reach their correct target sites in the vertebrate central nervous system (CNS). This is a fundamental problem in neuroscience. The delineation of how this is done normally should be important for understanding what goes wrong during developmental diseases of the nervous system and why regeneration following injury to the CNS is normally so poor. Evidence, from research funded by a grant to which this proposal is a continuation demonstrated that: 1) the early spinal cord of fish embryos is extremely simple consisting of a small number of identified neurons and non-neuronal cells; 2) growth cones of the five earliest neuronal classes reach their destinations in the CNS by following stereotyped, cell-specific pathways; 3) the behaviors of identified growth cones at specific sties suggest that identified cells may attract, inhibit, and direct their cell- specific turns. This proposal will test a number of hypotheses generated by this and other studies by laser ablating specific cells in the fish embryonic cord and assaying their effect by a combination of methods. This includes labeling single cells by intracellular dye injections, labeling all neurons or a specific subset of neurons with monoclonal antibodies, and electron microscopy. 1) Do growth cones receive directional cues from specific cells in their environment? 2) Do growth cones become sensitive to certain environmental cues only after interactions with other cells? 3) Can some cells specifically attract certain growth cones? 4) Can some cells specifically inhibit certain growth cones?
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