Using specific antibody markers and double-label immunofluorescence microscopy, we have followed the fate of progenitor cells in the sympathoadrenal (SA) sublineage of the neural crest in developing rat embryos. Such progenitors are first recognizable in the primordial sympathetic ganglia at embryonic day 11.5 (E11.5), when they express tyrosine hydroxylase. At this stage, the progenitors also coexpress neuronal markers such as SCG 10 and neurofilament, together with a series of chromaffin cell markers called SA 1-5 (Carnhan and Patterson, 1991 a). The observation of such doubly labeled cells is consistent with the hypothesis that these cells represent a common progenitor to sympathetic neurons and adrenal chromaffin cells. Subsequent to E 11.5, expression of the chromaffin markers is extinguished in the sympathetic ganglia but retained by cells within the adrenal gland. Concomitant with the loss of the SA 1-5 immunoreactivity in sympathetic ganglia, a later sympathetic neuron-specific marker, B2, appears. In dissociated cell suspensions, some B2+ cells that coexpress SA 1 are seen. This implies a switch in the antigenic phenotype of developing sympathetic neurons, rather than a replacement of one cell population by another. The SA 1----B2 transition does not occur for the majority of cells within the adrenal primordium. In vitro, most B2+ cells fail to differentiate into chromaffin cells in response to glucocorticoid. Instead, they continue to extend neurites and then die. Taken together, these data imply that the SA 1----B2 transition correlates with a loss of competence to respond to an inducer of chromaffin differentiation. Thus, the development of SA derivatives is controlled both by environmental signals and by changes in the ability of differentiating cells to respond to such signals.
Chromaffin cells and sympathetic neurons develop from a common neural crest-derived progenitor cell. The developmental fate of this cell differs depending upon whether it migrates to the sympathetic ganglion or to the adrenal gland primordium, suggesting that local environmental signals control its differentiation. Glucocorticoid (GC) is a good candidate for an important adrenal environmental signal. These steroids are known to regulate PNMT, an adrenal-specific enzyme. However, in vivo observations suggest that the adrenal microenvironment influences the phenotype of sympatho-adrenal progenitor cells as early as E14.5, 2 days before PNMT is first expressed by developing chromaffin cells. Using cDNA probes, we find that GC receptor mRNA can be detected in the embryonic adrenal at least one full day before the initial appearance of PNMT mRNA. This observation is compatible with the idea that the apparent early influence of the adrenal microenvironment reflects the action of GC on progenitors which have migrated into this environment. In support of this, we show that similar influences can be exerted by GC on PC12 cells, which contain GC receptor mRNA but do not express or induce PNMT mRNA. Taken together, these data suggest that other factors in addition to the presence of the GC receptor may be necessary for the developmental appearance of PNMT expression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.