{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:08:22Z","timestamp":1791306502660,"version":"4.3.1"},"reference-count":40,"publisher":"The Company of Biologists","issue":"1","license":[{"start":{"date-parts":[[1996,1,1]],"date-time":"1996-01-01T00:00:00Z","timestamp":820454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1996,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>c-ret encodes a tyrosine kinase receptor that is necessary for normal development of the mammalian enteric nervous system. Germline mutations in c-ret lead to congenital megacolon in humans, while a loss-of-function allele (ret.k \u2212) causes intestinal aganglionosis in mice. Here we examine in detail the function of c-ret during neurogenesis, as well as the lineage relationships among cell populations in the enteric nervous system and the sympathetic nervous system that are dependent on c-ret function. We report that, while the intestine of newborn ret.k \u2212 mice is devoid of enteric ganglia, the esophagus and stomach are only partially affected; furthermore, the superior cervical ganglion is absent, while more posterior sympathetic ganglia and the adrenal medulla are unaffected. Analysis of mutant embryos shows that the superior cervical ganglion anlage is present at E10.5, but absent by E12.5, suggesting that c-ret is required for the survival or prolif-eration of sympathetic neuroblasts. In situ hybridization studies, as well as direct labelling of cells with DiI, indicate that a common pool of neural crest cells derived from the postotic hindbrain normally gives rise to most of the enteric nervous system and the superior cervical ganglion, and is uniquely dependent on c-ret function for normal develop-ment. We term this the sympathoenteric lineage. In contrast, a distinct sympathoadrenal lineage derived from trunk neural crest forms the more posterior sympathetic ganglia, and also contributes to the foregut enteric nervous system. Overall, our studies reveal previously unknown complexities of cell lineage and genetic control mechanisms in the developing mammalian peripheral nervous system.<\/jats:p>","DOI":"10.1242\/dev.122.1.349","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T02:29:40Z","timestamp":1619404180000},"page":"349-358","source":"Crossref","is-referenced-by-count":375,"title":["Common origin and developmental dependence on <i>c-ret<\/i> of subsets of enteric and sympathetic neuroblasts"],"prefix":"10.1242","volume":"122","author":[{"given":"Pascale L.","family":"Durbec","sequence":"first","affiliation":[{"name":"1 Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena B.","family":"Larsson-Blomberg","sequence":"additional","affiliation":[{"name":"1 Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Schuchardt","sequence":"additional","affiliation":[{"name":"Columbia University, 2 Department of Genetics and Development, College of Physicians and Surgeons , New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Costantini","sequence":"additional","affiliation":[{"name":"Columbia University, 2 Department of Genetics and Development, College of Physicians and Surgeons , New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilis","family":"Pachnis","sequence":"additional","affiliation":[{"name":"1 Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1996,1,1]]},"reference":[{"key":"2025021322321669200_DEVELOP_122_1_349C1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0092-8674(88)90391-1","article-title":"Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons","volume":"53","author":"Alpert","year":"1988","journal-title":"Cell"},{"key":"2025021322321669200_DEVELOP_122_1_349C2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev.ne.16.030193.001021","article-title":"Molecular control of cell fate in the neural crest: the sympathoadrenal lineage","volume":"16","author":"Anderson","year":"1993","journal-title":"Annu. Rev. Neurosci"},{"key":"2025021322321669200_DEVELOP_122_1_349C3","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1096\/fasebj.8.10.8050669","article-title":"Stem cells and transcription factors in the development of the mammalian neural crest","volume":"8","author":"Anderson","year":"1994","journal-title":"FASEB J"},{"key":"2025021322321669200_DEVELOP_122_1_349C4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0012-1606(89)90217-0","article-title":"Transient catecholaminergic (TC) cells in the vagus nerves and bowel of fetal mice: relationship to the development of enteric neurons","volume":"132","author":"Baetge","year":"1989","journal-title":"Dev. Biol"},{"key":"2025021322321669200_DEVELOP_122_1_349C5","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0012-1606(90)90391-U","article-title":"Transiently catecholaminergic (TC) cells in the bowel of the fetal rat: precursors of noncatecholaminergic enteric neurons","volume":"141","author":"Baetge","year":"1990","journal-title":"Dev. Biol"},{"key":"2025021322321669200_DEVELOP_122_1_349C6","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/0092-8674(94)90018-3","article-title":"Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons","volume":"79","author":"Baynash","year":"1994","journal-title":"Cell"},{"key":"2025021322321669200_DEVELOP_122_1_349C7","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1242\/dev.120.3.613","article-title":"Induction of a second neural axis by the mouse node","volume":"120","author":"Beddington","year":"1994","journal-title":"Development"},{"key":"2025021322321669200_DEVELOP_122_1_349C8","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1242\/dev.119.3.597","article-title":"Sympathetic neuroblasts undergo a developmental switch in trophic dependence","volume":"119","author":"Birren","year":"1993","journal-title":"Development"},{"key":"2025021322321669200_DEVELOP_122_1_349C9","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/BF00502095","article-title":"Combined immunostaining of neurofilaments, neuron specific enolase, GFAP, and S-100: A possible means for assessing the morphological and functional status of the enteric nervous system","volume":"82","author":"Bishop","year":"1985","journal-title":"Histochemistry"},{"key":"2025021322321669200_DEVELOP_122_1_349C10","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1242\/dev.121.2.333","article-title":"Hox genes and the evolution of vertebrate axial morphology","volume":"121","author":"Burke","year":"1995","journal-title":"Development"},{"key":"2025021322321669200_DEVELOP_122_1_349C11","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/0012-1606(91)90273-6","article-title":"Evidence that enteric neurons may derive from the sympathoadrenal lineage","volume":"148","author":"Carnahan","year":"1991","journal-title":"Dev. 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Neurosci"},{"key":"2025021322321669200_DEVELOP_122_1_349C32","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1242\/dev.118.4.1049","article-title":"Regulative capacity of the cranial neural tube to form neural crest","volume":"118","author":"Scherson","year":"1993","journal-title":"Development"},{"key":"2025021322321669200_DEVELOP_122_1_349C33","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/367380a0","article-title":"Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret","volume":"367","author":"Schuchardt","year":"1994","journal-title":"Nature"},{"key":"2025021322321669200_DEVELOP_122_1_349C34","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1242\/dev.111.4.857","article-title":"Vital dye labelling demonstrates a sacral neural crest contribution to the enteric nervous system of chick and mouse embryos","volume":"111","author":"Serbedzija","year":"1991","journal-title":"Development"},{"key":"2025021322321669200_DEVELOP_122_1_349C35","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1242\/dev.116.2.297","article-title":"Vital dye analysis of cranial neural crest cell migration in the mouse embryo","volume":"116","author":"Serbedzija","year":"1992","journal-title":"Development"},{"key":"2025021322321669200_DEVELOP_122_1_349C36","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/0092-8674(94)90048-5","article-title":"Functions of the neurotrophins during nervous system development: what the knockouts are teaching us","volume":"77","author":"Snider","year":"1994","journal-title":"Cell"},{"key":"2025021322321669200_DEVELOP_122_1_349C37","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0306-4522(90)90364-A","article-title":"Ontogeny of the neuronal intermediate filament protein, peripherin, in the mouse embryo","volume":"36","author":"Troy","year":"1990","journal-title":"Neuroscience"},{"key":"2025021322321669200_DEVELOP_122_1_349C38","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1242\/dev.119.3.881","article-title":"The mouse homeodomain protein Phox2 regulates Ncam promoter activity in concert with Cux\/CDP and is a putative determinant of neurotransmitter phenotype","volume":"119","author":"Valarche","year":"1993","journal-title":"Development"},{"key":"2025021322321669200_DEVELOP_122_1_349C39","first-page":"75","article-title":"Whole mount in situ hybridization of vertebrate embryos","volume-title":"In In Situ Hybridization: a Practical Approach","author":"Wilkinson","year":"1992"},{"key":"2025021322321669200_DEVELOP_122_1_349C40","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/cne.901010212","article-title":"The origin of intrinsic gagnlia of trunk viscera from vagal neural crest in the chick embryo","volume":"101","author":"Yntema","year":"1954","journal-title":"J. C omp. Neurol"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/122\/1\/349\/3068163\/develop_122_1_349.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/122\/1\/349\/3068163\/develop_122_1_349.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T22:33:09Z","timestamp":1739485989000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/122\/1\/349\/38888\/Common-origin-and-developmental-dependence-on-c"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,1,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1996,1,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.122.1.349","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,1,1]]}}}