CONTROL OF NEUROTRANSMITTER PHENOTYPE IN THE EMBRYO

在我的实验室进行的研究已经证明了在大鼠中存在 细胞群的胚胎-位于肠间充质中， 几个颅感觉和背根神经节-短暂表达 儿茶酚胺（CA）表型的方面。 发育中的肠道细胞， 例如，在一个实施例中，具有酪氨酸羟化酶（T-OH）、多巴胺B-羟化酶、CA 荧光，和一个特定的，高亲和力的CA的摄取过程。 在 此外，它们对母体糖皮质激素升高有反应， 神经生长因子与T-OH水平增加和 CA性状的表达。 利用这些瞬时CA群体， 计划调查控制维护（或损失）的因素，或 神经递质表型表达。 具体而言，该计划是1） 在体内和体外研究糖皮质激素作用于 肠细胞，2）通过以下方式确定肠中瞬时CA细胞的命运： CA性状的药理学延长和同时检测 已知存在于成人肠道中的其他NT，3）确定 胚胎肠中的瞬时神经递质表达，4）确定 肠间充质支持CA性状的能力，以及5）检查 颅感觉神经节中短暂的T-OH阳性细胞， 表型命运和对激素和环境因素的反应， 体内和体外。

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. 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 glugocorticoid hormones and nerve growth factor 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.