In the early embryo, the first fate decision separates the trophectoderm from the inner cell mass (ICM). Subsequently, the ICM segregates into epiblast (Epi) and primitive endoderm (PrE), but how do cells decide which of these two fates to adopt? Claire Chazaud, Geneviève Dupont and co-workers address this question in the early mouse embryo (see p. ), using both experimental and modelling approaches. It is known that the FGF signalling pathway is involved in this fate decision and also that, while Epi cells express and depend on Nanog, PrE cells are defined by Gata6 expression. The authors complete the interaction network by demonstrating that Gata6 is not only expressed by the PrE but is also required for PrE specification. To understand the network in greater detail, the authors build a mathematical model incorporating the known interactions between these players. The model exhibits tristability, with steady states corresponding to cells displaying ICM, Epi or PrE fate, and is able to recapitulate experimental manipulations of the system, such as the removal of Nanog or Gata6 activity or the effects of altering FGF signalling. Moreover, this approach highlights a number of key features of the system – most notably the requirement for heterogeneity in FGF signalling levels and the self-organising nature of the process of fate determination in this context.
