TEAD4 role in trophectoderm commitment and development is not conserved in non-rodent mammals.

The first lineage differentiation in mammals gives rise to the inner cell mass (ICM) and the trophectoderm (TE). In mice, TEAD4 is a master regulation of TE commitment, as it regulates the expression of other TE-specific genes and its ablation prevents blastocyst formation, but its role in other mammals remains unclear. Herein, we have observed that TEAD4 ablation in two phylogenetically distant species (bovine and rabbits) does not impede TE differentiation, blastocyst formation and the expression of TE markers such as GATA3 and CDX2, although a reduced ICM cell number was observed in bovine TEAD4 KO blastocysts. Transcriptional analysis in bovine blastocysts revealed no major transcriptional effect of the ablation, although the expression of hypoblast and Hippo signalling-related genes tended to be decreased in KO embryos. Experiments were conducted in the bovine model to determine if TEAD4 was required for post-hatching development. TEAD4 KO spherical conceptuses showed normal development of the embryonic disc and TE, but hypoblast migration rate was reduced. At later stages of development (tubular conceptuses) no differences were observed between KO and WT conceptuses.