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Jørgensen, M.C.* ; de Lichtenberg, K.H.* ; Collin, C.A.* ; Klinck, R.* ; Ekberg, J.H.* ; Engelstoft, M.S.* ; Lickert, H. ; Serup, P.*

Neurog3-dependent pancreas dysgenesis causes ectopic pancreas in Hes1 mutant mice.

Development 145:dev163568 (2018)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Mutations in Hes1, a target gene of the Notch signalling pathway, lead to ectopic pancreas by a poorly described mechanism. Here, we use genetic inactivation of Hes1 combined with lineage tracing and live imaging to reveal an endodermal requirement for Hes1, and show that ectopic pancreas tissue is derived from the dorsal pancreas primordium. RNA-seq analysis of sorted E10.5 Hes1(+/+) and Hes1(-/-) Pdx1-GFP(+) cells suggested that upregulation of endocrine lineage genes in Hes1(-/-) embryos was the major defect and, accordingly, early pancreas morphogenesis was normalized, and the ectopic pancreas phenotype suppressed, in Hes1(-/-)Neurog3(-/-) embryos. In Mib1 mutants, we found a near total depletion of dorsal progenitors, which was replaced by an anterior Gcg(+) extension. Together, our results demonstrate that aberrant morphogenesis is the cause of ectopic pancreas and that a part of the endocrine differentiation program is mechanistically involved in the dysgenesis. Our results suggest that the ratio of endocrine lineage to progenitor cells is important for morphogenesis and that a strong endocrinogenic phenotype without complete progenitor depletion, as seen in Hes1 mutants, provokes an extreme dysgenesis that causes ectopic pancreas.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hes1 ; Ectopic Pancreas ; Neurog3 ; Morphogenesis; Foregut Progenitor Cells; Sonic-hedgehog; Endocrine Development; Transcription Factor; Islet Cells; Differentiation; Mouse; Expression; Reveals; Endoderm
Sprache
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 0950-1991
e-ISSN 1477-9129
Zeitschrift Development / Company of Biologists
Quellenangaben Band: 145, Heft: 7, Seiten: , Artikelnummer: dev163568 Supplement: ,
Verlag Company of Biologists
Verlagsort Bidder Building, Station Rd, Histon, Cambridge Cb24 9lf, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
POF Topic(s) 30204 - Cell Programming and Repair
Forschungsfeld(er) Stem Cell and Neuroscience
PSP-Element(e) G-500800-001
DOI 10.1242/dev.163568
WOS ID WOS:000447270100013
Scopus ID 85053229887
PubMed ID 30093553
Erfassungsdatum 2018-09-12
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