The long term goal of this research is to define in molecular detail the factors that control embryonic morphogenetic movements. Cells of the neural crest will be used to address fundamental questions concerning cell migration in the embryo. Neural crest cells give rise to a myriad of derivatives, each of which migrates and localizes to specific sites during embryogenesis. The previously accepted model for patterning neural crest derivatives proposed that neural crest cells are a pluripotent population of cells that migrate haphazardly into the various pathways and differentiate according to cues encountered in these paths. New evidence shows that an alternative mechanism guides melanoblasts (pigment cell precursors). Specifically: 1) melanoblasts are fate-specified prior to their migration from the neural tube, 2) only neural crest cells that are fate-specified as melanoblasts enter the dorsolateral path (i.e the path to the skin) and 3) under experimental conditions, melanoblasts are the only neural crest subpopulation that can exploit the dorsolateral path. This means that some neural crest subpopulations are specified prior to or shortly after they separate from the neural tube, and owing to molecular changes accompanying specification they are able to migrate in the appropriate path. In the next funding period we propose to extend this work by addressing the following Specific Aims: 1. To determine what molecular changes allow melanoblast migration into the dorsolateral path. 2. To determine what molecular changes control the specification of the melanoblast lineage. 3. To use a differential display strategy to determine what genes are expressed preferentially in the dorsal neural tube at the time that melanoblasts are being specified. 4. To determine whether prior specification of some neural crest subpopulations at the vagal level control pathway choice. Defects in neural crest morphogenesis are some of the most common birth defects and these studies may reveal their underlying basis.
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