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Understanding the past is to understand the present. Mammalian life, with all its complexity comes from a humble beginning of a single fertilized egg cell. Achieving this requires an enormous diversification of cellular function, the majority of which is generated through a series of cellular decisions during embryogenesis. The first decisions are made as the embryo prepares for implantation, a process that will require specialization of extra-embryonic lineages while preserving an embryonic one. In this mini-review, we will focus on the mouse as a mammalian model and discuss recent advances in the decision making process of the early embryo.

The temporal and spatial segregation of the two extra-embryonic cell lineages, trophectoderm and primitive endoderm (TE and PE respectively), from the pluripotent epiblast (EPI) during mammalian pre-implantation development are prerequisites for the successful implantation of the blastocyst. The mechanisms underlying these earliest stages of development remain a fertile topic for research and informed debate. In recent years novel roles for various transcription factors, polarity factors and signalling cascades have been uncovered. This mini-review seeks to summarise some of this work and to put it into the context of the regulative nature of early mammalian development and to highlight how the increasing evidence of naturally occurring asymmetries and heterogeneity in the embryo can bias specification of the distinct cell types of the blastocyst.