Department of Embryology, Faculty of Biology, The University of Warsaw, I. Miecznikowa, Warsaw, Poland.
Division of Developmental Biology and Medicine, The University of Manchester, Oxford Road, Manchester, United Kingdom.
PLoS One. 2019 Feb 8;14(2):e0212109. doi: 10.1371/journal.pone.0212109. eCollection 2019.
During preimplantation mouse development stages, emerging pluripotent epiblast (Epi) and extraembryonic primitive endoderm (PrE) cells are first distributed in the blastocyst in a "salt-and-pepper" manner before they segregate into separate layers. As a result of segregation, PrE cells become localised on the surface of the inner cell mass (ICM), and the Epi is enclosed by the PrE on one side and by the trophectoderm on the other. During later development, a subpopulation of PrE cells migrates away from the ICM and forms the parietal endoderm (PE), while cells remaining in contact with the Epi form the visceral endoderm (VE). Here, we asked: what are the mechanisms mediating Epi and PrE cell segregation and the subsequent VE vs PE specification? Differences in cell adhesion have been proposed; however, we demonstrate that the levels of plasma membrane-bound E-cadherin (CDH1, cadherin 1) in Epi and PrE cells only differ after the segregation of these lineages within the ICM. Moreover, manipulating E-cadherin levels did not affect lineage specification or segregation, thus failing to confirm its role during these processes. Rather, we report changes in E-cadherin localisation during later PrE-to-PE transition which are accompanied by the presence of Vimentin and Twist, supporting the hypothesis that an epithelial-to-mesenchymal transition process occurs in the mouse peri-implantation blastocyst.
在植入前的小鼠胚胎发育阶段，新兴的多能胚外上皮（Epi）和原始外胚层（PrE）细胞首先以“盐和胡椒”的方式分布在囊胚中，然后才分离成不同的层。由于这种分离，PrE 细胞定位于内细胞团（ICM）的表面，而 Epi 则被 PrE 细胞包裹在一侧，被滋养外胚层包裹在另一侧。在后期发育过程中，PrE 细胞的一个亚群从 ICM 迁移并形成壁内胚层（PE），而与 Epi 保持接触的细胞则形成内脏内胚层（VE）。在这里，我们提出了以下问题：介导 Epi 和 PrE 细胞分离以及随后的 VE 与 PE 特化的机制是什么？已经提出了细胞粘附的差异；然而，我们证明，只有在这些谱系在 ICM 内分离后，Epi 和 PrE 细胞中的质膜结合型 E-钙粘蛋白（CDH1，钙粘蛋白 1）水平才会有所不同。此外，操纵 E-钙粘蛋白水平并没有影响谱系特化或分离，因此不能证实其在这些过程中的作用。相反，我们报告了在稍后的 PrE 到 PE 过渡期间 E-钙粘蛋白定位的变化，这些变化伴随着波形蛋白和 Twist 的出现，支持了在小鼠植入前囊胚中发生上皮到间质转化过程的假说。
