{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:53:23Z","timestamp":1779342803732,"version":"3.51.4"},"reference-count":77,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,2,5]],"date-time":"2005-02-05T00:00:00Z","timestamp":1107561600000},"content-version":"vor","delay-in-days":2837,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioEssays"],"published-print":{"date-parts":[[1997,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are hereditary disorders related to the abnormal migration, proliferation or survival of neural crest cells and their derivatives. Hirschsprung disease is a frequent disorder of the enteric nervous system, resulting in intestinal obstruction. The multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural crest derivatives. Both diseases are associated with heterozygous mutations in the <jats:italic>RET<\/jats:italic> proto\u2010oncogene. <jats:italic>RET<\/jats:italic> encodes a transmembrane receptor tyrosine kinase expressed in neural crest lineages and whose ligand, glial\u2010cell\u2010line\u2010derived neurotrophic factor, has been very recently identified. <jats:italic>In vitro<\/jats:italic> expression studies demonstrate that while Hirschsprung disease mutations result in loss of function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2 mutations lead to its constitutive activation. Thus, the two \u2018faces\u2019 of RET, gain of function and loss of function, each lead to a different syndrome, respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or Hirschsprung disease, a developmental defect.<\/jats:p>","DOI":"10.1002\/bies.950190506","type":"journal-article","created":{"date-parts":[[2005,2,25]],"date-time":"2005-02-25T10:43:22Z","timestamp":1109328202000},"page":"389-395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Ret in human development and oncogenesis"],"prefix":"10.1002","volume":"19","author":[{"given":"Patrick","family":"Edery","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold","family":"Munnich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanislas","family":"Lyonnet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charis","family":"Eng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,5]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(74)80021-3"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320370317"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(88)91191-9"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/328527a0"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/328528a0"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.3.247"},{"key":"e_1_2_1_8_2","first-page":"1","article-title":"Stuhltr\u00e4gheit neugeborener infolge von dilatation und hypertrophic des colons","volume":"27","author":"Hirschsprung H.","year":"1888","journal-title":"Jahrb. 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