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Whereas mouse C-cells reside within the thyroid gland and derive from pharyngeal endoderm, avian C-cells are located within ultimobranchial glands and have been reported to derive from the neural crest. We use a comparative cell lineage tracing approach in a range of vertebrate model systems to resolve the ancestral embryonic origin of vertebrate C-cells. We find, contrary to previous studies, that chick C-cells derive from pharyngeal endoderm, with neural crest-derived cells instead contributing to connective tissue intimately associated with C-cells in the ultimobranchial gland. This endodermal origin of C-cells is conserved in a ray-finned bony fish (zebrafish) and a cartilaginous fish (the little skate, Leucoraja erinacea). Furthermore, we discover putative C-cell homologs within the endodermally-derived pharyngeal epithelium of the ascidian Ciona intestinalis and the amphioxus Branchiostoma lanceolatum, two invertebrate chordates that lack neural crest cells. Our findings point to a conserved endodermal origin of C-cells across vertebrates and to a pre-vertebrate origin of this cell type along the chordate stem.<\/jats:p>","DOI":"10.1242\/dev.202821","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T10:19:50Z","timestamp":1723025990000},"source":"Crossref","is-referenced-by-count":10,"title":["A pre-vertebrate endodermal origin of calcitonin-producing neuroendocrine cells"],"prefix":"10.1242","volume":"151","author":[{"given":"Jenaid M.","family":"Rees","sequence":"first","affiliation":[{"name":"University of Cambridge 1 Department of Zoology , , Cambridge CB2 3EJ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Kirk","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 Department of Zoology , , Cambridge CB2 3EJ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Gattoni","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 Department of Zoology , , Cambridge CB2 3EJ , UK"},{"name":"Columbia University 2 Department of Biological Sciences , , New York City, NY 10027 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Hockman","sequence":"additional","affiliation":[{"name":"University of Cape Town 3 Division of Cell Biology, Department of Human Biology , , Cape Town 7935 , South Africa"},{"name":"Neuroscience Institute, University of Cape Town 4 , Cape Town 7935 , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria A.","family":"Sleight","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 Department of Zoology , , Cambridge CB2 3EJ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan J.","family":"Ritter","sequence":"additional","affiliation":[{"name":"Vanderbilt School of Medicine 5 Department of Cell and Developmental Biology , , Nashville, TN 37240 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c8lia","family":"Benito-Gutierrez","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 Department of Zoology , , Cambridge CB2 3EJ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2977-3619","authenticated-orcid":false,"given":"Ela W.","family":"Knapik","sequence":"additional","affiliation":[{"name":"Vanderbilt School of Medicine 5 Department of Cell and Developmental Biology , , Nashville, TN 37240 , USA"},{"name":"Vanderbilt Genetics Institute, Vanderbilt School of Medicine 6 , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Gage","family":"Crump","sequence":"additional","affiliation":[{"name":"Eli and Edythe Broad Center for Regenerative Medicine 7 , Department of Stem Cell Biology and Regenerative Medicine , , Los Angeles, CA 90033 , USA"},{"name":"Keck School of Medicine, University of Southern California 7 , Department of Stem Cell Biology and Regenerative Medicine , , Los Angeles, CA 90033 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Fabian","sequence":"additional","affiliation":[{"name":"Eli and Edythe Broad Center for Regenerative Medicine 7 , Department of Stem Cell Biology and Regenerative Medicine , , Los Angeles, CA 90033 , USA"},{"name":"Keck School of Medicine, University of Southern California 7 , Department of Stem Cell Biology and Regenerative Medicine , , Los Angeles, CA 90033 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2062-3777","authenticated-orcid":false,"given":"J. 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