Fig. 6.

Initial steps in mouse ES cell differentiation. Summary of regulatory relationships between RA and Fgf pathways during ES cell differentiation, diagram adapted from Silva and Smith (Silva and Smith, 2008). Fgf/Erk signalling is required for loss of self-renewal and addition of RA stimulates Fgf8 transcription, which may ensure this step (indicated in grey). RA exposure also indirectly inhibits Fgf4 expression (indicated in grey). Cells lacking retinoid signalling accumulate in a Rex1-negative, Fgf5-positive state and exhibit greatly reduced neural differentiation, indicating that endogenous RA signalling normally promotes lineage commitment.