The role of the Notch signalling pathway in regulating the balance between neuronal and nonneuronal cells in sympathetic ganglia and the adrenal gland

Abstract

Sympathetic neurons and endocrine chromaffin cells of the adrenal medulla are catecholaminergic cells that derive from the neural crest. According to the classic model, they develop from a common sympathoadrenal (SA) progenitor that has the ability to differentiate into both sympathetic neurons and chromaffin cells depending on signals provided by their final environment. Our previous data revealed that a single premigratory neural crest cell can give rise to both sympathetic neurons and chromaffin cells, indicating that the fate decision between these cell types occurs after delamination. A more recent study demonstrated that at least half of chromaffin cells arise from a later contribution by Schwann cell precursors. Since Notch signalling is known to be implicated in the regulation of cell fate decisions, we investigated the early role of Notch signalling in regulating the development of neuronal and non-neuronal SA cells within sympathetic ganglia and the adrenal gland. To this end, we implemented both gain and loss of function approaches. Electroporation of premigratory neural crest cells with plasmids encoding Notch inhibitors revealed an elevation in the number of SA cells expressing the catecholaminergic enzyme tyrosine-hydroxylase, with a concomitant reduction in the number of cells expressing the glial marker P0 in both sympathetic ganglia and adrenal gland. As expected, gain of Notch function had the opposite effect. Numbers of neuronal and non-neuronal SA cells were affected differently by Notch inhibition depending on the time of its onset. Together our data show that Notch signalling can regulate the ratio of glial cells, neuronal SA cells and nonneuronal SA cells in both sympathetic ganglia and the adrenal gland.