Primitive endoderm (PE) and epiblast (EPI), which give rise to extra-embryonic tissues and the foetus, respectively, are derived from the inner cell mass (ICM) at day 3.5 (E3.5) of mouse embryogenesis and sort into distinct layers by E4.5. How the PE and EPI are initially specified is unclear, but one theory is that cell lineage history drives their fate. Now, using live cell tracing, Yojiro Yamanaka and co-workers report that they find no clear correlation between cell lineage history and PE/EPI segregation in mouse embryos; instead, FGF signalling directs this important segregation event (see p. 715). FGF/MAP kinase pathway inhibition shifts ICM cells towards an EPI fate, they show, whereas exogenously applied FGF shifts ICM cells towards PE. Furthermore, modulating FGF signalling during blastocyst maturation can still shift ICM cell fate, even though the mutually exclusive expression of lineage-specific transcription factors has begun. Thus, the researchers propose, stochastic and progressive specification of PE and EPI lineages occurs during blastocyst maturation in an FGF/MAP kinase signal-dependent manner.

© 2010.