The sympathoadrenal cell lineage: Specification, diversification, and new perspectives

AbstractDuring the past years considerable progress has been made in understanding the generation of cell diversity in the neural crest (NC). Sympathoadrenal (SA) cells constitute a major lineage among NC derivatives; they give rise to sympathetic neurons, neuroendocrine chromaffin cells, and the intermediate small intensely fluorescent (SIF) cells. The classic perception of how this diversification is achieved implies that (i) there is a common progenitor cell for sympathetic neurons and chromaffin cells, (ii) NC cells are instructed to a SA cell fate by signals derived from the wall of the dorsal aorta, especially bone morphogenetic proteins (BMP), and (iii) the local environments of secondary sympathetic ganglia and adrenal gland, respectively, are crucial for inducing differentiation of SA cells into sympathetic neurons and adrenal chromaffin cells. However, recent studies have suggested that the adrenal cortex is dispensable for the acquisition of a chromaffin cell fate. This review summarizes the current understanding of the development of SA cells. It covers the specification of SA cells from multipotent NC crest cells, the role of transcription factors during their development, the classic model of their subsequent diversification as well as alternative views for explaining the generation of endocrine versus neuronal SA derivatives