Figure 6
Model of temporal dynamics of ICM cell specification. Specification into Epi (red) or PrE (blue) is a progressive and asynchronous process that occurs for a majority of ICM cells (grey) between E3.25 and E3.75. The formation of Epi progenitors precedes that of PrE progenitors. ICM cell responsiveness to the modulation of FGF/ERK signaling varies over time. First, between E2.5 and E3.25, exogenous FGF4 treatment efficiently diverts unspecified ICM cell from Epi fate. Then, between E3.25 and E3.5, ICM cells are globally insensitive to modulation of FGF/ERK signaling. Between E3.5 and E3.75, remaining unspecified ICM cells but not already specified Epi progenitors are able to respond to exogenous FGF4 leading to a moderate shift in Epi/PrE specification upon treatment. FGF signaling and ERK phosphorylation increases in ICM cells and PrE progenitors during this time window. Accordingly, embryos become highly sensitive to FGF/ERK inhibition leading to the complete ICM conversion to Epi. During that period, proteasome degradation and transcription control NANOG and GATA6 levels in Epi and PrE progenitors. Downregulation of GATA6 levels in PrE progenitors upon FGF/ERK inhibition is partially mediated by the proteasome. After E3.75, responsiveness to exogenous FGF4 is lost when all ICM cells become specified while PrE progenitors are still able to respond to FGF/ERK inhibition.
