The enteric nervous system (ENS), which is derived from enteric neural crest cells
(ENCCs), represents the neuronal innervation of the intestine. Compromised ENCC migration
can lead to Hirschsprung disease, which is characterized by an aganglionic distal
bowel. During the craniocaudal migration of ENCCs along the gut, we find that their
proliferation is greatest as the ENCC wavefront passes through the ceca, a pair of
pouches at the midgut-hindgut junction in avian intestine. Removal of the ceca leads
to hindgut aganglionosis, suggesting that they are required for ENS development. Comparative
transcriptome profiling of the cecal buds compared with the interceca region shows
that the non-canonical Wnt signaling pathway is preferentially expressed within the
ceca. Specifically, WNT11 is highly expressed, as confirmed by RNA in situ hybridization,
leading us to hypothesize that cecal expression of WNT11 is important for ENCC colonization
of the hindgut. Organ cultures using embryonic day 6 avian intestine show that WNT11
inhibits enteric neuronal differentiation. These results reveal an essential role
for the ceca during hindgut ENS formation and highlight an important function for
non-canonical Wnt signaling in regulating ENCC differentiation.
