Abstract
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.
Highlights
The formation of extraembryonic lineages that facilitate the establishment of mother-foetus connections and participate in the interchange of nutrients and metabolites within the maternal uterine environment is a prerequisite for the successful development of mammalian embryos [1]
At the early blastocyst stage (E3.5, 30–63 cells), primitive endoderm (PrE) marker expression was observed in some inner cell mass (ICM) cells, and in accordance with our previous results, we could distinguish three populations: GFP-ve cells, classified as Epi precursors; GFP+ve low cells, which may contribute to both Epi and PrE lineages; and GFP+ve high cells, classified as PrE precursors [6, 51]
Our observations indicate that at the early blastocyst stage, PrE and Epi cells do not differ in membrane E-cadherin distribution and do not polarise when lining the blastocyst cavity
Summary
The formation of extraembryonic lineages that facilitate the establishment of mother-foetus connections and participate in the interchange of nutrients and metabolites within the maternal uterine environment is a prerequisite for the successful development of mammalian embryos [1]. PrE precursors differentiate within the inner cell mass (ICM) of mammalian blastocysts before implantation. To that differentiation, the remaining ICM cells specify the embryonic epiblast (Epi) lineage, which will give rise to the body of the future foetus after implantation [3,4]. At the early blastocyst stage (~32 cells) PrE- and Epi-specific genes (Gata and Nanog, respectively) are co-expressed in all ICM cells [5,6]. Starting from around the 64-cell mid-blastocyst stage, downregulation of the genes involved in pluripotency in PrE precursors and downregulation of Gata in Epi precursors initiate appropriate cell fate specification and the emergence of precursors of both lineages, which are initially randomly distributed throughout the ICM [5,6,7,8]. The VE, in turn, partially develops into the endodermal membrane of the visceral yolk sac [17] and assists in gas and nutrient exchange between the growing embryo and its environment, as well as in patterning of the embryo [1]
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