During preimplantation development, the inner cell mass differentiates into robust ratios of epiblast and primitive endoderm (PrE) cells, which express NANOG and GATA6, respectively. FGF signalling is known to function in this process, but how it controls proportional differentiation has been unclear. Now, Christian Schröter and colleagues investigate population-level function of FGF in this process. The authors use embryonic stem cells in an elegant in vitro system coupled with genetic systems to show the effect of FGF signalling on differentiation after transient induction of GATA4 expression. In a minimal medium, similar proportions of epiblast and PrE differentiate regardless of the level of GATA4 induction. When exposed to exogenous FGF4, however, more PrE cells differentiate. The authors identify cell-intrinsic regulatory links between FGF and GATA factors, and show through loss-of-function and rescue experiments that regulated FGF expression is required for proportional differentiation. By testing the spatial range of FGF4 signalling, the researchers show that GATA6-positive PrE emerges through short-range, FGF4-based cell-cell communication. Finally, they show that FGF4 expressed by wild-type cells can help to regenerate properly portioned cell identities after the loss of a single cell type from the population. Together, these data indicate that FGF signalling generates and maintains cell type proportions.
