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首页> 外文期刊>Development >Oct4 regulates the embryonic axis and coordinates exit from pluripotency and germ layer specification in the mouse embryo.
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Oct4 regulates the embryonic axis and coordinates exit from pluripotency and germ layer specification in the mouse embryo.

机译:OCT4调节胚胎轴和坐标从小鼠胚胎中的多能性和种子层规格出口。

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摘要

Lineage segregation in the mouse embryo is a finely controlled process dependent upon coordination of signalling pathways and transcriptional responses. Here we employ a conditional deletion system to investigate embryonic patterning and lineage specification in response to loss of Oct4. We first observe ectopic expression of Nanog in Oct4-negative postimplantation epiblast cells. The expression domains of lineage markers are subsequently disrupted. Definitive endoderm expands at the expense of mesoderm; the anterior-posterior axis is positioned more distally and an ectopic posterior-like domain appears anteriorly, suggesting a role for Oct4 in maintaining the embryonic axis. Although primitive streak forms in the presumptive proximal-posterior region, epithelial-to-mesenchymal transition is impeded by an increase of E-cadherin, leading to complete tissue disorganisation and failure to generate germ layers. In explant and in vitro differentiation assays, Oct4 mutants also show upregulation of E-cadherin and Foxa2, suggesting a cell-autonomous phenotype. We confirm requirement for Oct4 in self-renewal of postimplantation epiblast ex vivo Our results indicate a role for Oct4 in orchestrating multiple fates and enabling expansion, correct patterning and lineage choice in the postimplantation epiblast.
机译:小鼠胚胎中的谱系偏析是依赖于信号传导途径和转录反应的细化控制过程。在这里,我们采用条件删除系统来调查胚胎图案化和谱系规范,以应对OCT4的损失。我们首先观察到Oct4阴性后后期外血管细胞中纳米的异位表达。随后破坏了谱系标记的表达域。最终的内胚层以牺牲中胚层的牺牲膨胀;前后轴线更远侧定位,并且异位后域出现在前面,表明OCT4在维持胚胎轴方面的作用。尽管在推定近端区域中的原始条纹形式形成上皮 - 间充质转变,但通过增加E-cadherin来阻抗,导致完全组织紊乱和未能产生胚层。在外植体和体外分化测定中,OCT4突变体还显示出E-Cadherin和FoxA2的上调,表明细胞 - 自主表型。我们确认Oct4在后期后期的Epiblast前体内的要求我们的结果表明Oct4在协调多个命运方面的作用,并在后期外部植物中开展扩展,正确的图案化和谱系选择。

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