Enteric nervous system development: Analysis of the selective developmental potentialities of vagal and sacral neural crest cells using quail-chick chimeras

The majority of the enteric nervous system (ENS) is derived from vagal neur al crest cells (NCC). For many years, the contribution from a second region of the neuraxis (the sacral neural crest) to the ENS has been less clear, with conflicting reports appearing in the literature. To resolve this longs tanding issue, we documented the spatiotemporal migration and differentiati on of vagal and sacral-derived NCC within the developing chick embryo using quail-chick grafting: and antibody labelling. Results showed that vagal NC C colonised the entire length of the gut in a rostrocaudal direction. The h indgut, the region of the gastrointestinal tract most frequently affected i n developmental disorders, was found to be colonised in a complex manner. V agal NCC initially migrated within the submucosa, interval to the circular muscle layer, before colonising the myenteric plexus region. In contrast, s acral NCC, which colonised the hindgut in a caudorostral direction, were pr imarily located in the myenteric plexus region from where they subsequently migrated to the submucosa. We also observed that sacral NCC migrated into the hindgut in significant numbers only after vagal-derived cells had colon ised the entire length of the gut. This suggested that to participate in EN S formation, sacral cells may require an interaction with vagal-derived cel ls, or with factors or signalling molecules released by them or their proge ny. To investigate this possible inter-relationship, we ablated sections of vagal neural crest (NC) to prevent the rostrocaudal migration of ENS precu rsors and, thus, create an aganglionic hindgut model. In the same NC ablate d animals, quail-chick sacral NC grafts were performed. In the absence of v agal-derived ganglia, sacral NCC migrated and differentiated in an apparent ly normal manner. Although the numbers of sacral cells within the hindgut w as slightly higher in the absence of vagal-derived cells, the increase was not sufficient to compensate for the lack of enteric ganglia. As vagal NCC appear to be more invasive than sacral NCC, since they colonise the entire length of the gut, we investigated the ability of transplanted vagal cells to colonise the hindgut by grafting the vagal NC into the sacral region. We found that when transplanted, vagal cells retained their invasive capacity and migrated into the hindgut in large numbers. Although sacral-derived ce lls normally contribute a relatively small number of precursors to the post -umbilical gut, many heterotopic vagal cells were found within the hindgut enteric plexuses at; much earlier stages of development than normal. Hetero topic grafting of invasive vagal NCC into the sacral neuraxis may, therefor e, be a means of rescuing an aganglionic hindgut phenotype. Anat Rec 262:16 -28, 2001. (C) 2001 Wiley-Liss, Inc.