Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse.
Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse.
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DOI：
10.1242/dev.014357
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发表时间：
2008-02
期刊：
影响因子：
--
通讯作者：
Robertson EJ
中科院分区：
文献类型：
--
作者：
Arnold SJ;Hofmann UK;Bikoff EK;Robertson EJ
T-box转录因子Eomesodermin（Eomes）在脊椎动物胚胎的胚层诱导和模式化中是一个重要的组成部分。在小鼠中，Eomes对于滋养外胚层谱系的发育是必不可少的，并且Eomes功能丧失突变体在植入时停止。在这里，我们使用了一种新的Eomes条件等位基因来测试Eomes在胚胎中的功能。Eomes缺陷的胚胎表达Fgf 8和其下游目标蜗牛在正常水平，但令人惊讶的是不能下调E-钙粘蛋白。因此，Eomes功能丧失有效地和深刻地阻止EMT和伴随的中胚层分层。标志物分析以及命运定位和嵌合体研究首次证明了Eomes是定形内胚层谱系的特化所必需的。我们还描述了Eomes/Nodal双杂合子的发育异常，并证明这些表型反映了Eomes和Nodal在不同组织部位的相互作用。总的来说，我们的实验证实，Eomes是小鼠前后轴形成、EMT和定形内胚层特化的关键调节因子。
The T-box transcription factor eomesodermin (Eomes) has been implicated as an important component in germ layer induction and patterning in vertebrate embryos. In the mouse, Eomes is essential for development of the trophectoderm lineage and Eomes loss-of-function mutants arrest at implantation. Here, we have used a novel Eomes conditional allele to test Eomes functions in the embryo proper. Eomes-deficient embryos express both Fgf8 and its downstream target Snail at normal levels but surprisingly fail to downregulate E-cadherin. Eomes functional loss thus efficiently and profoundly blocks EMT and concomitant mesoderm delamination. Marker analysis as well as fate-mapping and chimera studies demonstrate for the first time that Eomes is required for specification of the definitive endoderm lineage. We also describe developmental abnormalities in Eomes/Nodal double heterozygotes, and demonstrate that these phenotypes reflect Eomes and Nodal interactions in different tissue sites. Collectively, our experiments establish that Eomes is a key regulator of anteroposterior axis formation, EMT and definitive endoderm specification in the mouse.
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