Formation and malformation of the enteric nervous system

To clarify pathogenetic mechanisms of congenital malformations of the ENS, the formation of the ENS was investigated in chicken and murine embryos. The experimental work was concentrated on several aspects of the interaction between neural crest cells and the enteric microenvironment. We investigated (a) whether enteric neural crest cells are sensitive to ischemia; (b) whether the migration substrates in aneuronal bowel persist when neural crest cell colonization is postponed; (c) when neural crest cells colonize various parts of murine bowel; (d) when and where the Is/Is gene affects neural crest cell colonization; (e) which axial level of the neuraxis provides precursor cells for enteric neurons; (f) how neural crest cells are directed to the future sites of the enteric ganglia; (g) whether neural crest cells proliferate during, migration and homing in the bowel. Hirschsprung's disease has a heterogeneous etiology that has been related to genetic, chromosomal, and other yet unknown factors. Family studies suggest genetic factors in the etiology of Hirschsprung's disease but there is little evidence of simple Mendelian inheritance. It seems that Hirschsprung's disease is an example of sexmodified multifactorial inheritance.