Transmitter phenotypic expression in the embryo.

The initial appearance and development of noradrenergic and adrenergic phenotypic characters was studied in the rat embryo by immunocytochemical methods. Tyrosine hydroxylase and dopamine-beta-hydroxylase (noradrenergic enzymes) appeared at 11.5 days of gestation (Day E 11.5; 27-30 somites) in sympathetic ganglion primordia and in cells of the gut. While tyrosine hydroxylase and dopamine beta-hydroxylase immunoreactivity increased progressively in ganglion primordia, the enzymes disappeared in the gut cells after E 13.5. However, the gut cells themselves persisted, as indicated by the high-affinity uptake of noradrenaline (norepinephrine). Consequently, initial appearance of noradrenergic characters does not ensure persistence and subsequent development, indicating that early phenotypic expression is a mutable process. This contention was supported by the observations that pharmacological stress of pregnant rats in the form of reserpine, or treatment with glucocorticoids, prolonged the appearance of catecholamines in the gut cells. Thus, maternal-embryonic relations in general, and maternal glucocorticoids in particular, may influence embryonic phenotypic expression. Treatment of embryos with nerve growth factor also prolonged the appearance of noradrenergic characters in the gut cells. Expression of the adrenergic phenotype was apparently regulated differently from noradrenergic expression, since phenylethanolamine-N-methyltransferase (PNMT), the adrenaline-(epinephrine)-synthesizing enzyme, was undetectable in ganglion primordia and gut cells. PNMT initially appeared at E 17.5 in cells which had migrated to be adrenal anlage. Extensive studies suggest that the initial appearance of PNMT occurs independently of glucocorticoid regulation, while subsequent development is dependent on corticoids.