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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Neurog3-dependent pancreas dysgenesis causes ectopic pancreas in Hes1 mutant mice.
Development 145:dev163568 (2018)
Verlagsversion
DOI
PMC
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
ISSN (print) / ISBN
0950-1991
e-ISSN
1477-9129
Zeitschrift
Development / Company of Biologists
Quellenangaben
Band: 145,
Heft: 7,
Artikelnummer: dev163568
Verlag
Company of Biologists
Verlagsort
Bidder Building, Station Rd, Histon, Cambridge Cb24 9lf, England
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Stem Cell Research (ISF)