The neural crest is the embryonic progenitor of a wide array of adult cell types including the neurons of the sympathetic, parasympathetic, enteric, and most sensory ganglia, the cells of the adrenal medulla, Schwann cells, cranial connective tissue including the teeth and major bones of the head and face, and the melanocytes of the skin and irides. The overall objective of our research is to understand the control of the differentiation of neural crest cells into neurons. In this proposal we focus on the ontogeny of catecholamine (CA)-containing cells, some of which also contain somatostatin-like immunoreactivity (SLI) or neuropeptide Y immunoreactivity (NPY). We will take advantage of the fact that CA+, SLI+, and NPY+ cells differentiate when neural crest cells are grown in tissue culture to study several aspects of this development. First, we will determine the detailed phenotype of the CA+, SLI+, and NPY+ cells which develop using specific antibodies as phenotypic markers. Second, we will operationally characterize, identify, and enrich for the neural crest cell populations which contain the precursors of the CA+, SLT+, and NPY+ cells. Third, we will determine the extent of the differentiation of the CA+ cells which develop in our cultures by comparing their properties to those of three types of CA+ neural crest-derived cells which arise in vivo. These three CA+ cell types are principal sympathetic neurons, small intensely fluorescent cells, and chromaffin cells of the adrenal medulla. This comparison will analyze ultrastructural phenotypic markers, antibody markers at the light microscopic level, and investigate the cellular responses to Nerve Growth Factor and glucocorticoid hormones. In addition to their value to basic neuroscience these studies may prove relevant to studies of congenital birth defects including several phakomatoses and neurocristopathic disorders in which abnormal neural crest development is implicated.
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