The Role and Mechanism of TEAD4 in Preimplantation Embryonic Development in Mice and Cattle

Abstract

AbstractTead4, a critical transcription factor expressed during preimplantation development, is essential for the expression of trophectoderm-specific genes in mice. However, the functional mechanism ofTead4in mouse preimplantation development and its conservation across mammals remain unclear. Here, we report that Tead4 is a crucial transcription factor necessary for blastocyst formation in mice. Disruption ofTead4through base editing results in developmental arrest at the morula stage. Additionally, RNA-seq analysis reveals dysregulation of 670 genes inTead4knockout embryos. As anticipated,Tead4knockout leads to a decrease in trophectoderm genesCdx2andGata3. Intriguingly, we observed a reduction in Krt8, suggesting that Tead4 influences the integrity of the trophectoderm epithelium in mice. More importantly, we noted a dramatic decrease in nuclear Yap in outside cells forTead4-deficient morula, indicating that Tead4 directly regulates Hippo signaling. In contrast, bovine embryos withTEAD4depletion could still develop to blastocysts with normal expression ofCDX2,GATA3, andSOX2, albeit with a decrease in total cell number and ICM cell number. In conclusion, we propose that Tead4 regulates mouse blastocyst formation via Krt8 and Yap, both of which are critical regulators of mouse preimplantation development.