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

Abstract

The ETS superfamily transcription factors Elf5 and Ets2 have both been implicated in the maintenance of the extraembryonic ectoderm (ExE) of the mouse embryo. While homozygous mutants of either gene result in various degrees of ExE tissue loss, heterozygotes are without phenotype. We show here that compound heterozygous mutants exhibit a phenotype intermediate to that of the more severe Elf5-/- and the milder Ets2-/- mutants. Functional redundancy is shown via commonalities in expression patterns, in target gene expression, and by partial rescue of Elf5-/- mutants through overexpressing Ets2 in an Elf5-like fashion. A model is presented suggesting the functional division of the ExE region into a proximal and distal domain based on gene expression patterns and the proximal to distal increasing sensitivity to threshold levels of combined Elf5 and Ets2 activity.

Morphological and Gene Expression Changes in Cattle Embryos from Hatched Blastocyst to Early Gastrulation Stages after Transfer of In Vitro Produced Embryos

“…Indeed as discussed previously, we see no cattle DVH and whereas the mouse epiblast radius increases by over 100% per day (e.g. 50 μm to over 100 μm between E5.5 and 6.5 [49]), the cattle epiblast increases only by 35% a day (from Fig 1A; d/dx of e 0.30x ). Lastly, cattle epiblast expression of BMP4 is not seen in mice [25].…”

“… a For mouse embryos proximal-distal length has been doubled to reflect a “flattening out” of the cup shaped epiblast; references for epiblast diameters: [17, 47, 49]. …”

Changes in the enhancer landscape during early placental development uncover a trophoblast invasion gene-enhancer network

“…For the Ets family of transcription factors, we see that Elf3, Elf4, and Elf5 are also differentially expressed between e7.5 and e9.5 placentas. This could indicate that these TFs have overlapping roles with Ets2; recently it has been shown that Ets2 can partially rescue Elf5−/− mutants, which have defects in extraembryonic tissue [64]. In order to fully understand the interplay among these TF family members, and their specific contributions to trophoblast invasion, additional genetic studies will be needed.…”

The ETS Family Transcription Factors Etv5 and PU.1 Function in Parallel To Promote Th9 Cell Development

“…However, PU.1 and ETV5 are from different sub-families. This is not without precedent and ETS2 and ELF5, factors from distinct sub-families, cooperate in development (41). Some of this redundancy is clearly dependent on overlapping binding specificities of the family-defining DNA binding domain (42).…”