Early Sacral Neural Crest Migration in Dominant megacolon Mouse Embryos

Abstract

Hirschsprung’s disease, or congenital megacolon, is the most common gastrointestinal motility disorder in newborns. The prominent feature of Hirschsprung’s disease is an abnormal dilatation of the distal colon resulting from a regional absence or reduction of enteric ganglion cells. It has been known that all intrinsic enteric ganglion cells are derived from neural crest cells, which migrate along defined pathways from the neural tube (embryonic central nervous system) to the gut during embryonic development. Recent studies on avian embryos have also indicated that neural crest cells at the sacral level contribute a significant number of enteric neurons to the hindgut, the region of the gut where aganglionosis is usually detected in Hirschsprung’s disease. In the present study, we aimed to identify anomalies in the early migration of sacral neural crest cells in the Dominant megacolon(Dom) mouse mutant, a model for Hirschsprung’s disease. A combination of whole embryo culture, in situ cell labeling and histochemical staining was used to follow the early sacral neural crest cell migration. In the wild-type embryos, when sacral neural crest cells caudal to the 24th somite were labeled at embryonic day 10.0 (E10.0), labeled cells were found in the mesenchyme on the two sides of neural tube and many of them resided in the region of dorsal root ganglia at E11.0. Some of them were also found in the region around the dorsal aorta. In embryos heterozygous and homozygous for Dom, similar distribution and migratory pattern were found, indicating that the early migration of sacral neural crest cells was not affected in the mutant. Our results hence implicated that anomalies in the early sacral crest cell migration are unlikely to be a cause of aganglionosis in the hindgut of the Dom mutant.