Colonisation of the gut by neural crest‐derived enteric nervous system precursors: migration pathways and developmental potentials

Abstract

The neurons and glia of the enteric nervous system (ENS) are derived from vagal and sacral neural crest cells (NCC). Vagal (hindbrain) NCC migrate from the dorsal neural tube, accumulate in the caudal branchial arches, enter the foregut and colonise the entire gut in a rostro-caudal direction, reaching the terminal hindgut of the chick at embryonic day 7.5. Sacral NCC, which arise caudal to the 28th pair of somites, initially form the nerve of Remak in the chick, then enter the gut after it has been colonised by vagal cells. The contribution of sacral cells to the ENS is restricted to the post-umbilical gut, and mainly the hindgut. It therefore appears that vagal and sacral NCC have different ENS developmental potentials, since vagal cells form most of the ENS along the entire gut, whereas sacral NCC provide a limited number of cells to the hindgut. This idea is further supported by heterotopic grafting experiments: transplanting vagal NCC into the sacral region results in rapid and extensive gut colonisation, whereas transplanting sacral cells into the vagal region results in diminished colonisation, compared with vagal NCC. To better understand the differences in ENS developmental potentials between these two populations, we analysed the expression of ENS signalling molecules in vagal and sacral NCC, and show that increasing the expression of the receptor tyrosine kinase RET in sacral NCC leads to increased gut colonisation.