The successful development from a single-cell zygote into a complex 
multicellular organism requires precise coordination of multiple cell-fate 
decisions. The very first of these is lineage specification into the inner cell 
mass (ICM) and trophectoderm (TE) during mammalian preimplantation development. 
In mouse embryos, transcription factors (TFs) such as Oct4, Sox2, and Nanog are 
enriched in cells of ICM, which gives rise to the fetus and yolk sac. 
Conversely, TFs such as Cdx2 and Eomes become highly upregulated in TE, which 
contribute to the placenta. Here, we review the current understanding of key 
transcriptional control mechanisms and genes responsible for these distinct 
differences during the first cell lineage specification. In particular, we 
highlight recent insights gained through advances in genome manipulation, live 
imaging, single-cell transcriptomics, and loss-of-function studies.