One of the earliest events in mammalian development occurs when the inner cell mass segregates into two distinct cell populations: the epiblast (Epi) and the primitive ectoderm (PrE). Much is known regarding the molecular and signalling pathways that regulate this early fate decision, but what remains unclear is how these inputs are integrated into the molecular circuitry in order to regulate precisely the temporal and spatial emergence of these two cell lineages. Now, on p. 4205, Alfonso Martinez Arias and colleagues investigate this question using multicolour single-cell quantitative assays and mathematical modelling, and demonstrate a dual role for FGF/MAPK signalling in the decision between PrE and Epi cell fates. Firstly, the authors show that in order for GATA factors to activate the PrE gene expression programme, the FGF/MAPK pathway must be inhibited. Secondly, the authors demonstrate that MAPK signalling also sets the threshold level of GATA transcription factors required...

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