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At the time of implantation, the early mouse embryo consists of three distinct cell lineages: the epiblast (EPI), primitive endoderm (PrE), and trophectoderm (TE). Here we will focus on the EPI and PrE cell lineages, which arise within the inner cell mass (ICM) of the blastocyst. Though still poorly understood, our current understanding of the mechanisms underlying this lineage allocation will be discussed. It was originally thought that lineage choice was strictly controlled by the position of a cell within the ICM. However, it is now believed that the EPI and PrE lineages are defined both by their position and by the expression of lineage-specific transcription factors. Interestingly, these lineage-specific transcription factors are initially co-expressed in early ICM cells, suggesting an initial multi-lineage priming state. Thereafter, lineage-specific transcription factors display a mutually exclusive salt-and-pepper distribution that reflects cell specification of the EPI or PrE fates. Later on, lineage segregation and likely commitment are completed with the sequestration of PrE cells to the surface of the ICM, which lies at the blastocyst cavity roof. We discuss recent advances that have focused on elucidating how the salt-and-pepper pattern is established and then resolved within the ICM, leading to the correct apposition of cell lineages in preparation for implantation.

Cell Lineage Allocation Within the Inner Cell Mass of the Mouse Blastocyst