title: Aganglionosis in rodents.
abstract: The etiology of aganglionosis of the bowel remains controversial. Initial embryological studies in chicks, mice, and humans suggested the defect was in the migratory capacity of the vagal neural crest cells. This traditional theory has recently been challenged by the demonstration of a defect in the local microenvironment and the suggestion that neural crest cells migrate normally until they reach the terminal defective segment of bowel which then excludes them. To contribute to this debate we studied three rodent animal models using histological, "in vivo" (kidney capsule), and "in vitro" (tissue culture) techniques. The results suggest that there is no discernible difference between mutant and normal embryos in the early migration from the vagal neural crest to the stomach. Migration through the small bowel is normal in mutant mice, but is slowed in the rat. In both strains of mice the migration of enteric precursors into the mutant colon is slowed over an extended period of time, such that a difference between normal and mutants is evidenced well before the final aganglionic region is reached. Aganglionosis is the result either of a defect in vagal neural crest migration or in the microenvironment over an extended area of the bowel and not just in the terminal aganglionic colon. There are changes in the appearance of mutant enteric neurons in tissue culture and some alterations in the gut mesenchyme; it remains to be determined which is the primary event.
authors.affiliation: Department of Pediatric Surgery, Westmead Hospital, Australia.
authors.forename: D T
authors.initials: DT
authors.lastname: Cass
authors.forename: A L
authors.initials: AL
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Morthorpe
mesh_terms: D000818:Animals; D046508:Culture Techniques; D005260:Female; D006627:Hirschsprung Disease / Q000196:embryology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D051381:Rats; D011922:Rats, Mutant Strains