Dual origin of enteric neurons in vagal Schwann cell precursors and the sympathetic neural crest

Significance The enteric nervous system of vertebrates arises mostly from a rostral portion of the neural crest, encapsulated by the term “vagal.” We show that the “vagal crest” is in fact a juxtaposition of two completely different types of cells: Schwann cell precursors associated with the vagus nerve, which provide esophageal neurons, and the rostral-most trunk crest, which also forms sympathetic ganglia and locally overshoots the aorta to colonize most of the gut. Moreover, in line with the known dependency of both Schwann cell precursors and trunk crest on the ErbB3 tyrosine receptor kinase and its ligand Neuregulin1, we discover that the enteric nervous system is also atrophic in ErbB3 mutants, with potential relevance to Hirschsprung disease, a congenital hypoganglionosis.