Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo

In female mammals, conception is a complex process that involves several stages. First, an egg is released from the ovary and travels along a tube called the oviduct, where sperm from a male may fertilize it. If the egg is fertilized, the newly formed embryo moves into the womb, where it will then implant into the walls. In mice, it takes around four days for the embryo to implant and during this time, the cells in the embryo divide several times and start to specialize to form distinct cell types called lineages. The first two lineages to form are known as the inner cell mass and the trophectoderm. The inner cell mass forms a ball of cells within the embryo and contains the precursors of all cells that build the animal’s body. The trophectoderm forms a layer that surrounds the inner cell mass and will become part of the placenta (the organ that supplies the embryo with nutrients while it is in the womb). The embryo can organize these lineages without any instructions from the mother. However, it is still not clear when the cells start to differ from each other, and when they ‘commit’ to stay in these lineages. Cells in the inner cell mass and trophectoderm have different gene expression profiles, meaning that many genes display different levels of activity in these two lineages. Posfai et al. use a technique called single-cell RNA sequencing to analyse gene activity as the inner cell mass and trophectoderm form in mouse embryos. By measuring changes in gene activity, it is possible to track their development and show which genes change expression levels when each lineage specifies and commits. The experiments reveal that the inner cell mass and trophectoderm lineages develop at different times. As the inner cell mass forms, cells adopt the inner cell mass ‘identity’ before they commit to remaining in this lineage, revealing a window of time where different signals could still change the fate of the cells. However, when the early trophectoderm cells show the first signs of specialization, they also commit to their new identity at the same time. These findings suggest that the different timings at which these cell lineages form might provide embryos with the means to organize their own cells. An important future challenge is to understand exactly how the cells commit to their fate.