Significance Intercellular signaling pathways strongly regulate gene expression in uncommitted precursor stem cells, but the mechanisms through which these signaling pathways regulate gene targets often remain unclear. We address this question in mouse embryonic stem cells (mESCs) and highlight the importance of AU-rich element mRNA-binding proteins as regulatory intermediates of intercellular signaling. We show that the FGF/Erk MAP kinase signaling pathway strongly influences the expression of Brf1, a member of the Zfp36 protein family that is known to bind and destabilize its mRNA targets. Brf1 physically binds many pluripotency and differentiation-associated mRNAs. Moderate changes in its expression compromise self-renewal capacity and bias fate commitment, thus providing a posttranscriptional link between intercellular signaling activity and gene expression in mESCs.