Nodal species embryonic visceral endoderm and sustains pluripotent cells in the epiblast before overt axial patterning
Nodal species embryonic visceral endoderm and sustains pluripotent cells in the epiblast before overt axial patterning
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DOI：
10.1242/dev.02413
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发表时间：
2006-07-01
期刊：
影响因子：
4.6
通讯作者：
Constam, Daniel B.
中科院分区：
文献类型：
--
作者：
Mesnard, Daniel;Guzman-Ayala, Marcela;Constam, Daniel B.
哺乳动物胚胎的前后极性是在原肠胚形成期间确定的，当时原始外胚层的原始祖细胞被招募到原始条纹中形成中胚层和内胚层。在另一端，这一过程被先前在远端内脏内胚层（DVE）诱导的信号所抑制。DVE和原始条纹的形成以及AP轴的定位都依赖于TGF β家族成员Nodal及其蛋白转化酶Furin和Pace4。在这里，我们发现Nodal和Furin最初在原始内胚层中与一些DVE标记物如Lefty1和Hex一起共表达。然而，随着胚胎外胚层（ExE）的出现，DVE的形成被暂时抑制。在这一阶段，Nodal活性对于确定胚胎VE和将Furin的表达限制在胚胎外区域至关重要。在植入过程中，Nodal的激活对于维持Oct4、Nanog和Foxd3等多能性决定因素，以及在诱导DVE和胚层形成之前刺激卵筒伸长也是必要的。我们得出结论，Nodal在原始内胚层中已经被激活，但只有在促进胚胎VE和外胚层中多能祖细胞的扩增后才诱导出功能性的DVE。
Anteroposterior (AP) polarity in the mammalian embryo is specified during gastrulation when naive progenitor cells in the primitive ectoderm are recruited into the primitive streak to form mesoderm and endoderm. At the opposite pole, this process is inhibited by signals previously induced in distal visceral endoderm (DVE). Both DVE and primitive streak formation, and hence positioning of the AP axis, rely on the TGF beta family member Nodal and its proprotein convertases Furin and Pace4. Here, we show that Nodal and Furin are initially co-expressed in the primitive endoderm together with a subset of DVE markers such as Lefty1 and Hex. However, with the appearance of extra-embryonic ectoderm (ExE), DVE formation is transiently inhibited. During this stage, Nodal activity is essential to specify embryonic VE and restrict the expression of Furin to the extra-embryonic region. Activation of Nodal is also necessary to maintain determinants of pluripotency such as Oct4, Nanog and Foxd3 during implantation, and to stimulate elongation of the egg cylinder, before inducing DVE and germ layer formation. We conclude that Nodal is already activated in primitive endoderm, but induces a functional DVE only after promoting the expansion of embryonic VE and pluripotent progenitor cells in the epiblast.