GENERATION OF CELL DIVERSITY IN THE PERIPHERAL AUTONOMIC NERVOUS-SYSTEM - THE SYMPATHOADRENAL CELL LINEAGE REVISITED

Based on recent evidence from in vitro and gene knock-out/knock-in stu dies this short review summarizes the molecular scenario underlying th e development of autonomic neurons from the neural crest. The focus is on the sympathoadrenal (SA) cell lineage. While migrating ventrally p recursors of this cell lineage are exposed to signals from notochord/v entral neural tube probably including the protein sonic hedgehog. Thes e and signals in the region of the dorsal aorta (members of the family of bone morphogenetic proteins), where SA progenitor cells subsequent ly assemble, are essential for the induction of the adrenergic phenoty pe. SA progenitor cells subsequently differentiate into paravertebral and prevertebral sympathetic neurons, intra-and extra-adrenal chromaff in cells and intermediate SIF (small intensely fluorescent) cells. Bas ed on in vitro studies with isolated SA and chromaffin progenitor cell s glucocorticoids have been claimed as essential for suppressing a neu ronal commitment and channeling SA cells towards the chromaffin phenot ype. Unexpectedly, mice deficient for a functional glucocorticoid rece ptor possess the full complement of adrenal chromaffin cells at birth. We present a hypothetical scenario consistent with these data, in whi ch chromaffin cell development would be the default pathway in the SA cell lineage, while development into a neuronal direction requires spe cific growth factor signaling, which is probably distinct for paravert ebral and prevertebral sympathetic neurons.