Making the first decision: lessons from the mouse

Pre‐implantation development encompasses a period of 3–4 days over which the mammalian embryo has to make its first decision: to separate the pluripotent inner cell mass (ICM) from the extra‐embryonic epithelial tissue, the trophectoderm (TE). The ICM gives rise to tissues mainly building the body of the future organism, while the TE contributes to the extra‐embryonic tissues that support embryo development after implantation. This review provides an overview of the cellular and molecular mechanisms that control the critical aspects of this first decision, and highlights the role of critical events, namely zytotic genome activation, compaction, polarization, asymmetric cell divisions, formation of the blastocyst cavity and expression of key transcription factors.