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In the first part, we describe the critical features of two principal abnormalities of ENS development: Hirschsprung's disease (HSCR) and intestinal neuronal dysplasia type B (INDB) in humans, and the similar abnormalities in animals. These represent the extremes of the diagnostic spectrum: HSCR has agreed and unequivocal diagnostic criteria, whereas the diagnosis and even existence of INDB as a clinical entity is highly controversial. The difficulties in diagnosis and treatment of both these conditions are discussed. We then review the genes now known which, when mutated or deleted, may cause defects of ENS development. Many of these genetic abnormalities in animal models give a phenotype similar or identical to HSCR, and were discovered by studies of humans and of mouse mutants with similar defects. The most important of these genes are those coding for molecules in the GDNF intercellular signaling system, and those coding for molecules in the ET-3 signaling system. However, a range of other genes for different signaling systems and for transcription factors also disturb ENS formation when they are deleted or mutated. In addition, a large proportion of HSCR cases have not been ascribed to the currently known genes, suggesting that additional genes for ENS development await discovery. <\/jats:p>","DOI":"10.1007\/s10024-001-0142-y","type":"journal-article","created":{"date-parts":[[2003,12,2]],"date-time":"2003-12-02T21:39:20Z","timestamp":1070401160000},"page":"224-247","source":"Crossref","is-referenced-by-count":181,"title":["Enteric Nervous System: Development and Developmental Disturbances\u2014Part 1"],"prefix":"10.1177","volume":"5","author":[{"given":"Donald","family":"Newgreen","sequence":"first","affiliation":[{"name":"Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, 3052, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Melbourne, 3010, Victoria, 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