Arnold Sebastian J, Hofmann Ulf K, Bikoff Elizabeth K, Robertson Elizabeth J
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Development. 2008 Feb;135(3):501-11. doi: 10.1242/dev.014357. Epub 2008 Jan 2.
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.
T 盒转录因子胚外中胚层决定因子（Eomes）被认为是脊椎动物胚胎中胚层诱导和模式形成的重要组成部分。在小鼠中，Eomes 对于滋养外胚层谱系的发育至关重要，Eomes 功能缺失突变体在着床时停滞发育。在此，我们使用了一种新型的 Eomes 条件性等位基因来检测 Eomes 在胚胎本身中的功能。Eomes 缺陷型胚胎正常水平表达 Fgf8 及其下游靶标 Snail，但令人惊讶的是未能下调 E-钙黏蛋白。因此，Eomes 功能丧失有效且深刻地阻断了上皮-间质转化（EMT）以及伴随的中胚层分层。标记分析以及命运图谱和嵌合体研究首次证明，Eomes 是确定内胚层谱系特化所必需的。我们还描述了 Eomes/Nodal 双杂合子中的发育异常，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。总体而言，我们的实验表明，Eomes 是小鼠前后轴形成、EMT 和确定内胚层特化的关键调节因子。
