Fig. 7.

Model for changing cell states during pre-implantation development. Epiblast precursors, characterised by Nanog expression, represent a naïve totipotent state that can convert to primed PrE precursors in response to Erk activation. The properties of PrE precursors predisposes them to cell sorting, after which positional signals reinforce commitment to a PrE fate. Likewise, eventual loss of Nanog in epiblast precursors, which are protected from differentiation signals by their inside position, leads to epiblast commitment. We speculate that, in the absence of Erk activation, naïve epiblast precursors can also pass through a trophoblast precursor state that becomes reinforced by positional signals.