Dr. Weston will exploit the avian neural crest, which provides an experimentally accessible population of pluripotent embryonic cells that undergoes a characteristic sequence of restrictions of developmental potential. Phenotypically distinct crest-derived subpopulations can be detected at early stages of development using sensitive cell type-specific markers. Some of these subpopulations appear to arise from developmentally restricted, but functionally undifferentiated embryonic cells. Although the existence of developmentally restricted precursors has been inferred, they cannot now be identified directly. Therefore to characterize the initial appearance and ultimate fate of these cells, we propose: 1) to identify subpopulations of crest-derived cells that have distinct, limited developmental potentials using specifically identified monoclonal antibody markers; and 2) to characterize the normal developmental appearance of immunochemically identified cells, and the subsequent expression by these cells of other phenotypic traits characteristic of crest derivatives. To examine early restriction of developmental potential, we propose; 3) to analyze the response of identified precursors to environmental factors, including an assessment of a) the responses of a crest-derived neurogenic precursor subpopulation to specific growth and survival factors, and b) the normal responses of nascent neurons to environmental cues. %%% The developmental potential of embryonic cells becomes progressively more restricted during embryogenesis. The mechanisms by which this occurs remain to be elucidated. In this study Dr. Weston will address the important issue of how this diversity is generated, stabilized and propagated within cellular lineages during embryonic development.
