Distinct mechanisms regulate Cdx2 expression in the blastocyst and in trophoblast stem cells

Abstract

The first intercellular differences during mammalian embryogenesis arise in the blastocyst, producing the inner cell mass and the trophectoderm. The trophectoderm is the first extraembryonic tissue and does not contribute to the embryo proper, its differentiation instead forming tissues that sustain embryonic development. Crucial roles in extraembryonic differentiation have been identified for certain transcription factors, but a comprehensive picture of the regulation of this early specification is still lacking. Here, we investigated whether the regulatory mechanisms involved in Cdx2 expression in the blastocyst are also utilized in the postimplantation embryo. We analyzed an enhancer that is regulated through Hippo and Notch in the blastocyst trophectoderm, unexpectedly finding that it is inactive in the extraembryonic structures at postimplantation stages. Further analysis identified other Cdx2 regulatory elements including a stem-cell specific regulatory sequence and an element that drives reporter expression in the trophectoderm, a subset of cells in the extraembryonic region of the postimplantation embryo and in trophoblast stem cells. The cross-comparison in this study of cis-regulatory elements employed in the blastocyst, stem cell populations and the postimplantation embryo provides new insights into early mammalian development and suggests a two-step mechanism in Cdx2 regulation.

Self‐organization of human iPS cells into trophectoderm mimicking cysts induced by adhesion restriction using microstructured mesh scaffolds

“…Starting as small transparent buds, the cysts expand as they sweep preexisting cells outwards to become bubble-like transparent structures anchored on a membrane on mesh. We have confirmed the expression of a key trophectoderm marker, Cdx2 (Rayon et al, 2016), and also examined the morphological architecture of the cysts, which we have determined consist of partitioned interior cavities closely resembling that of blastocysts, in particular late blastocyst. In addition, we have demonstrated that anchored cysts may exhibit an invasion behavior, which is a key feature of post-implantation trophectoderm.…”

Extracellular glucose levels in cultures of undifferentiated mouse trophoblast stem cells affect gene expression during subsequent differentiation with replicable cell line-dependent variation

“…3B–E). We then investigated the levels of H3K27Ac and H3K27me3 at the following genomic regions; around the transcriptional start sites (TSS) for Cdx2 and Prl3d1 , upstream of Cdx2 (UP), the regulatory regions of Cdx2 effective in blastocysts (TEE) [33], and in TSCs (#1 and #3) [34], the putative binding sites for Hand1 (TSS (HAND1)), AP1 (AP1) and Gata2 (GATA) in the regulatory region of rodent Prl3d1 [35,36,37], and a control region (TSS of Actb ) (Fig. 3C and 3D).…”

Follistatin treatment modifies DNA methylation of the CDX2 gene in bovine preimplantation embryos

“…CDX2 expression is temporally and spatially regulated in preimplantation embryos (Cockburn & Rossant, 2010; Niwa et al, 2005; Rayon et al, 2016). Several transcriptional and epigenetic mechanisms control CDX2 expression during early embryonic development (Saha et al, 2013; Senner, Krueger, Oxley, Andrews, & Hemberger, 2012; Yuan et al, 2009).…”