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首页> 外文期刊>Development >Neurog3-dependent pancreas dysgenesis causes ectopic pancreas in Hes1 mutant mice
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Neurog3-dependent pancreas dysgenesis causes ectopic pancreas in Hes1 mutant mice

机译：Neurog3依赖性胰腺功能生物发生导致HES1突变小鼠中的异位胰腺

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摘要

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.
机译：HES1中的突变，陷波信号传导途径的靶基因，通过描述的机制导致异位胰腺。在这里，我们使用HES1的遗传失活与谱系追踪和实时成像结合，以揭示对HES1的内胚层需求，并表明异位胰腺组织来自背部胰腺原始。 RNA-SEQ分析的分类E10.5 HES1（+ / +）和HES1（ - / - ）PDX1-GFP（+）细胞表明HES1（ - / - ）胚胎中的内分泌谱系基因的上调是主要的缺陷和，因此，早期胰腺发生正常化，并且异位胰腺表型抑制在HES1（ - / - ）神经胶3（ - / - ）胚胎中。在MIB1突变体中，我们发现背部祖细胞的近总耗尽，其被前型GCG（+）延伸。我们的结果表明，异常的形态发生是异位胰腺的原因，并且内分泌分化计划的一部分是机械性地参与的困难。我们的研究结果表明，内分泌谱系与祖细胞的比例对于形态发生而言是重要的，并且在HES1突变体中看到的没有完全祖细胞耗尽的强型内分泌表型引起了引起异位胰腺的极端渗透。

著录项

  • 来源
    《Development》 |2018年第17期|共11页
  • 作者

    Jorgensen Mette C.; de Lichtenberg Kristian H.; Collin Caitlin A.; Klinck Rasmus; Ekberg Jeppe H.; Engelstoft Maja S.; Lickert Heiko; Serup Palle;

  • 作者单位

    Univ Copenhagen NNF Ctr Stem Cell Biol DanStem Fac Hlth &

    Med Sci DK-2200 Copenhagen Denmark;

    Univ Copenhagen NNF Ctr Stem Cell Biol DanStem Fac Hlth &

    Med Sci DK-2200 Copenhagen Denmark;

    Univ Copenhagen NNF Ctr Stem Cell Biol DanStem Fac Hlth &

    Med Sci DK-2200 Copenhagen Denmark;

    Novo Nordisk AS Dept User Res &

    Commun Brennum Pk 1 DK-3400 Hillerod Denmark;

    Univ Copenhagen NNF Ctr Basic Metab Res Sect Metab Receptol Lab Mol Pharmacol Fac Hlth &

    Med Sci;

    Univ Copenhagen NNF Ctr Basic Metab Res Sect Metab Receptol Lab Mol Pharmacol Fac Hlth &

    Med Sci;

    Helmholtz Zentrum Munchen Inst Stem Cell Res D-85764 Neuherberg Germany;

    Univ Copenhagen NNF Ctr Stem Cell Biol DanStem Fac Hlth &

    Med Sci DK-2200 Copenhagen Denmark;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 人体形态学;
  • 关键词

    Hes1; Ectopic pancreas; Neurog3; Morphogenesis;

    机译：HES1;异位胰腺;神经痛3;形态发生;

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