title: A chicken model of pharmacologically-induced Hirschsprung disease reveals an unexpected role of glucocorticoids in enteric aganglionosis.
abstract: The enteric nervous system originates from neural crest cells that migrate in chains as they colonize the embryonic gut, eventually forming the myenteric and submucosal plexus. Failure of the neural crest cells to colonize the gut leads to aganglionosis in the terminal gut, a pathological condition called Hirschsprung disease (HSCR) in humans, also known as congenital megacolon or intestinal aganglionosis. One of the characteristics of the human HSCR is its variable penetrance, which may be attributable to the interaction between genetic factors, such as the endothelin-3/endothelin receptor B pathway, and non-genetic modulators, although the role of the latter has not well been established. We have created a novel HSCR model in the chick embryo allowing to test the ability of non-genetic modifiers to alter the HSCR phenotype. Chick embryos treated by phosphoramidon, which blocks the generation of endothelin-3, failed to develop enteric ganglia in the very distal bowel, characteristic of an HSCR-like phenotype. Administration of dexamethasone influenced the phenotype, suggesting that glucocorticoids may be environmental modulators of the penetrance of the aganglionosis in HSCR disease.
authors.affiliation: Centre Interdisciplinaire de Recherche Biomédicale (CIRB), Collège de France, 75005 Paris, France Chaire de Médecine Expérimentale, Collège de France, 75005 Paris, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Gasc
authors.affiliation: Centre Interdisciplinaire de Recherche Biomédicale (CIRB), Collège de France, 75005 Paris, France Chaire de Médecine Expérimentale, Collège de France, 75005 Paris, France Centre de Recherche St-Antoine UMRS-938, INSERM-Université Pierre et Marie Curie, Paris 6, 75012 Paris, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Clemessy
authors.affiliation: Centre Interdisciplinaire de Recherche Biomédicale (CIRB), Collège de France, 75005 Paris, France Chaire de Médecine Expérimentale, Collège de France, 75005 Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Corvol
authors.affiliation: Centre Interdisciplinaire de Recherche Biomédicale (CIRB), Collège de France, 75005 Paris, France Chaire de Médecine Expérimentale, Collège de France, 75005 Paris, France UMR 7365 CNRS-Université de Lorraine, IMoPA, Faculté de Médecine, 54500 Vandoeuvre-lès-Nancy, France herve.kempf@inserm.fr.
authors.forename: Hervé
authors.initials: H
authors.lastname: Kempf
keywords: Chick embryo; Endothelin; Enteric nervous system; Glucocorticoids; Hirschsprung disease
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