Ets2-dependent trophoblast signalling is required for gastrulation progression after primitive streak initiation

Abstract

Although extraembryonic ectoderm trophoblast signals the embryo for primitive streak initiation, a prerequisite for gastrulation, it is unknown whether it also signals for the progression of gastrulation after primitive streak initiation. Here, using Ets2 À / À mice, we show that trophoblast signalling is also required in vivo for primitive streak elongation, completion of intraembryonic mesoderm epithelial-mesenchymal transition and the development of anterior primitive streak derivatives such as the node. We show that Ets2-dependent trophoblast signalling is required for the maintenance of high levels of Nodal and Wnt3 expression in the epiblast and for the induction of Snail expression in the primitive streak, between embryonic day 6.3 and 6.7. Within extraembryonic ectoderm trophoblast, Ets2 maintains the expression of the transcription factors Elf5, Cdx2 and Eomes, and that of the signalling molecule Bmp4. We propose a model that provides a genetic explanation as to how Ets2 in trophoblast mediates the progression of gastrulation within the epiblast.

Developmental plasticity, cell fate specification and morphogenesis in the early mouse embryo

“…Ets2 promotes the Elf5/Cdx2/Eomes expression circuit within the ExE. Accordingly, Ets2 knockout embryos implant but show severely reduced development of the TE lineages [95,96]. …”

Elf5 and Ets2 maintain the mouse extraembryonic ectoderm in a dosage dependent synergistic manner

“…We interpret the retention of Ascl2 in such embryos to mean that the DiExE is retained sufficiently long to allow for Ascl2 expression in remaining DiExE and/or EPC tissue. This is supported at least in type II Ets2 mutants where the DiExE marker Elf5 is expressed at E6.3 but lost by E6.7 (Polydorou and Georgiades, 2013). Conversely, while full Ets2 activity is able to mask the effect of losing one Elf5 allele, it cannot compensate for losing both Elf5 alleles.…”

“…These are Elf5 and Ets2 (Yamamoto et al, 1998;Donnison et al, 2005;Georgiades and Rossant, 2006;Wen et al, 2007;Odiatis and Georgiades, 2010;Polydorou and Georgiades, 2013). Notably, both these genes code for proteins belonging to the 26 proteins making up the superfamily of ETS transcription factors (Blake et al, 2014).…”

Transcriptional regulators of the trophoblast lineage in mammals with hemochorial placentation

“…Both ELF5 (Donnison, et al 2005, Ng, et al 2008) and ETS2 (Georgiades and Rossant 2006) are expressed in the trophoblast stem/progenitor cells within the ExE and are essential for their maintenance (Ng, et al 2008, Wen, et al 2007). ExE development is defective in both ELF5 and ETS2-null embryos causing defective reciprocal interactions of ExE with the embryonic ectoderm leading to impaired gastrulation, embryo patterning and embryonic death (Donnison, et al 2005, Georgiades and Rossant 2006, Polydorou and Georgiades 2013). Maintenance and differentiation of trophoblast stem/progenitor cells within the ExE is also regulated by transcription factor POU class 5 homeobox 1 (POU5F1) (Sebastiano, et al 2010).…”