[Endothelin B receptor system and Hirschsprung disease]

Abstract

Hirschsprung disease is a congenital malformation caused by the absence of ganglion cells in the myenteric and submucosal neural plexuses of gut. Mutations in the endothelin-Beta receptor (EDNRB) and endothelin-3(EDN3) genes as well as in the RET, glial-cell-derived neurotrophic factor and sox 10 genes have been shown to be responsible for this disease. These genes are involved in the development of intestinal neural crest derivatives. Recent studies have shown that EDNRB is expressed in neural crest cells before and through their migration into gut, whilst EDN3 is expressed in the mesenchymal cells. EDN3 acts as both a proliferative and also a differentiation factor in the development of neural crest cells. These reports support the hypothesis that EDN3 is an environmental factor which influences the migrating neural crest cells which express EDNRB.