Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development

Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development
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DOI:
10.1016/j.ydbio.2005.11.006
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发表时间:
2006-02-01
影响因子:
2.7
通讯作者:
Zaret, KS
Zaret, KS
中科院分区:
生物学3区
文献类型:
--
作者:
Bort, R;Signore, M;Zaret, KS

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关于胚胎肝、肺和胰腺祖细胞从内胚层上皮中出现并启动器官发生的机制知之甚少。了解这一过程及其遗传控制可以帮助我们深入了解个体发育、发育异常和组织再生。我们发现,肝内胚层细胞被特化后不久,它们就会经历从柱状、肠道形态到假复层形态的转变,并在细胞分裂过程中伴随着“运动间核迁移”(INM)。 INM 是假复层上皮的标志,也是神经祖细胞从神经上皮中出现的过程。我们发现肝内胚层而非神经上皮向假复层上皮的转变取决于同源框基因 Hex 的细胞自主活性。在缺乏 Hex 的情况下,肝内胚层细胞存活,但保持柱状、简单的上皮表型,并异位表达 Shh 和中肠上皮的其他特征基因。因此,Hex 通过促进向假复层上皮的转变来促进内胚层器官发生,这反过来又允许成肝细胞进入基质环境并继续分化。 (c) 2005 Elsevier Inc. 保留所有权利。
Little is known about the mechanism by which embryonic liver, lung, and pancreas progenitor cells emerge from the endodermal epithelium to initiate organogenesis. Understanding this process and its genetic control provides insight into ontogeny, developmental abnormalities, and tissue regeneration. We find that shortly after hepatic endoderm cells are specified, they undergo a transition from a columnar, gut morphology to a pseudostratified morphology, with concomitant "interkinetic nuclear migration" (INM) during cell division. INM is a hallmark of pseudostratified epithelia and the process used by neural progenitors to emerge from the neural epithelium. We find that the transition of the hepatic endoderm, but not the neural epithelium, to a pseudostratified epithelium is dependent upon the cell-autonomous activity of the homeobox gene Hex. In the absence of Hex, hepatic endoderm cells survive but maintain a columnar, simple epithelial phenotype and ectopically express Shh and other genes characteristic of the midgut epithelium. Thus, Hex promotes endoderm organogenesis by promoting the transition to a pseudostratified epithelium, which in turn allows hepatoblasts to emerge into the stromal environment and continue differentiating. (c) 2005 Elsevier Inc. All rights reserved.