CONTROL OF NEUROTRANSMITTER PHENOTYPE IN THE EMBRYO

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Studies performed in my laboratory have documented the existence in rat embryos of cell populations -- located in intestinal mesenchyme and in several cranial sensory and dorsal root ganglia -- which transiently express aspects of the catecholamine (CA) phenotype (14-19). Cells in developing gut, e.g., possess tyrosine hydroxylase (T-OH), dopamine B-hydroxylase, CA fluorescence, and a specific, high-affinity uptake process for CA's. In addition, they respond to elevated maternal glucocorticoid hormones (17, 18) and nerve growth factor (NGF, 21, 177) with increased levels of T-OH and a prolonged expression of CA traits. Utilizing these transiently CA populations we plan to investigate factors which control the maintenance (or loss) or neurotransmitter phenotypic expression. Specifically, the plan is to 1) investigate both in vivo and in vitro the site of glucocorticoid action on gut cells, 2) determine the fate of transiently CA cells in gut by pharmacological prolongation of CA traits and simultaneous detection of other NT's known to be present in adult gut, 3) determine the function of transient neurotransmitter expression in embryonic intestine, 4) determine the capacity of intestinal mesenchyme to support CA traits, and 5) examine transiently T-OH-positive cells in cranial sensory ganglia with respect to phenotypic fate and response to hormonal and environmental factors both in vivo and in vitro.