Figure 2: Specification of TE fate in mice. (a) Preimplantation embryo development in mice. After fertilization, the oosperm divides to form two blastomeres. The blastomeres constantly proliferate and then undergo cell polarization and compaction at the late 8-cell stage to form morula. The 8–16-cell division stage gives rise to inner (yellow) and outer (blue) cells that contribute, respectively, to the ICM and TE of the blastocyst. The primitive endoderm cell (green) lineage emerges from the ICM at the early blastula stage. At the late blastocyst stage, the mouse embryo gives rise to three tissues: TE, ICM, and primitive endoderm. (b) Key molecular pathways to bias ICM fate or TE fate in early mouse embryo. Between the late 2-cell and 4-cell stages, the high level of Carm1 biases the fate of ICM. Baf155 promotes TE specification and is negatively regulated by Carm1. At the late 8-cell stage, keratins function as asymmetrically inherited factors that specify the first TE cells of the embryo. At the 8–16-cell stage, Yap1 nuclear localization and interaction with the trophoblast -specific factor, Tead4, is the main signal for the specification of the TE. (c) Yap1 translocation to the nuclei determines TE specification at the 8–16-cell stage. The inhibition of the Hippo pathway promotes Yap1/Taz translocation to the nuclei, where they interact with Tead4 to activate the expression of target genes. ZGA: Zygotic gene activation; TE: Trophectoderm; ICM: Inner cell mass; PrE: Primitive endoderm; Epi: Epiblast.