title: Pathogenesis of Hirschsprung's disease and its variants: recent progress.
abstract: The enteric nervous system (ENS) is a complex network of interconnected neurons within the wall of the intestine that controls intestinal motility, regulates mucosal secretion and blood flow, and also modulates sensation from the gut. The cells that form the ENS in mammals are derived primarily from vagal neural crest cells. During the past decade there has been an explosion of information about genes that control the development of neural crest. Molecular-genetic analysis has identified several genes that have a role in the development of Hirschsprung's disease. The major susceptibility gene is RET, which is also involved in multiple endocrine neoplasia type 2. Recently, genetic studies have provided strong evidence in animal models that intestinal neuronal dysplasia (IND) is a real entity. HOX11L1 knockout mice and endothelin B receptor-deficient rats demonstrated abnormalities of the ENS resembling IND type B in humans. These findings support the concept that IND may be linked to a genetic defect.
authors.affiliation: Children's Research Centre, Our Lady's Hospital for Sick Children, University College Dublin, Ireland.
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
authors.forename: Toko
authors.initials: T
authors.lastname: Shinkai
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D016232:Endothelins / Q000235:genetics; D017615:Enteric Nervous System / Q000196:embryology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006609:High Mobility Group Proteins / Q000235:genetics; D006627:Hirschsprung Disease / Q000235:genetics* / Q000503:physiopathology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology; D055757:SOXE Transcription Factors; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D016232:Endothelins; C495039:GDNF protein, human; C491860:GFRA4 protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; C109220:NBPhox protein; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; C527925:Sox10 protein, rat; D014157:Transcription Factors; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases