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Johansson, E.* ; Andersson, L.B.* ; Örnros, J.* ; Carlsson, T.* ; Ingeson-Carlsson, C.* ; Liang, S.* ; Dahlberg, J.* ; Jansson, S.A.* ; Parrillo, L.* ; Zoppoli, P.* ; Barila, G.O.* ; Altschuler, D.L.* ; Padula, D. ; Lickert, H. ; Fagman, H.* ; Nilsson, M.*

Revising the embryonic origin of thyroid C cells in mice and humans.

Development 142, 3519-3528 (2015)
Verlagsversion DOI PMC
Closed
Creative Commons Lizenzvertrag
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail–chick chimeras involving fate mapping of neural crest cells to the ultimobranchial glands that regulate Ca2+ homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development involves a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing, we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. Like many gut endoderm derivatives, embryonic C cells were found to coexpress pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis, differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo, consistent with a growth-promoting role of Foxa1. In contrast to embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment downregulated Foxa2, foregoing epithelial-to-mesenchymal transition designated by loss of E-cadherin;bothFoxa2 andE-cadherinwere re-expressed atmetastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm and redefine the boundaries of neural crest diversification.The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Endoderm ; Foxa1 ; Foxa2 ; Medullary Thyroid Cancer ; Neural Crest ; Neuroendocrine
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 0950-1991
e-ISSN 1477-9129
Zeitschrift Development / Company of Biologists
Quellenangaben Band: 142, Heft: 20, Seiten: 3519-3528 Artikelnummer: , Supplement: ,
Verlag Company of Biologists
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Regeneration Research (IDR)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502300-001
PubMed ID 26395490
DOI 10.1242/dev.126581
WOS ID WOS:000366358700008
Scopus ID 84944754859
Erfassungsdatum 2015-10-31
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