title: Mouse models of Hirschsprung disease and other developmental disorders of the enteric nervous system: Old and new players.
abstract: Hirschsprung disease (HSCR, intestinal aganglionosis) is a multigenic disorder with variable penetrance and severity that has a general population incidence of 1/5000 live births. Studies using animal models have contributed to our understanding of the developmental origins of HSCR and the genetic complexity of this disease. This review summarizes recent progress in understanding control of enteric nervous system (ENS) development through analyses in mouse models. An overview of signaling pathways that have long been known to control the migration, proliferation and differentiation of enteric neural progenitors into and along the developing gut is provided as a framework for the latest information on factors that influence enteric ganglia formation and maintenance. Newly identified genes and additional factors beyond discrete genes that contribute to ENS pathology including regulatory sequences, miRNAs and environmental factors are also introduced. Finally, because HSCR has become a paradigm for complex oligogenic diseases with non-Mendelian inheritance, the importance of gene interactions, modifier genes, and initial studies on genetic background effects are outlined.
authors.affiliation: INSERM, U955, Equipe 6, F-94000 Creteil, France; Universite Paris-Est, UPEC, F-94000 Creteil, France. Electronic address: nadege.bondurand@inserm.fr.
authors.forename: Nadege
authors.initials: N
authors.lastname: Bondurand
authors.affiliation: Vanderbilt University Medical Center, Department of Medicine, 2215 Garland Ave, Nashville, TN 37232, USA. Electronic address: Michelle.southard-smith@vanderbilt.edu.
authors.forename: E Michelle
authors.initials: EM
authors.lastname: Southard-Smith
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000473:pathology*; D006627:Hirschsprung Disease / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D009432:Neural Crest / Q000196:embryology*; D015398:Signal Transduction
keywords: Enteric nervous system; Hirschsprung; Mouse models; Neural crest