Successful specification of the two mouse blastocyst inner cell mass (ICM) lineages (the primitive endoderm (PrE) and epiblast) is a prerequisite for continued development and requires active fibroblast growth factor 4 (FGF4) signaling. Previously, we identified a role for p38 mitogen-activated protein kinases (p38-MAPKs) during PrE differentiation, but the underlying mechanisms have remained unresolved. Here, we report an early blastocyst window of p38-MAPK activity that is required to regulate ribosome-related gene expression, rRNA precursor processing, polysome formation and protein translation. We show that p38-MAPK inhibition-induced PrE phenotypes can be partially rescued by activating the translational regulator mTOR. However, similar PrE phenotypes associated with extracellular signal-regulated kinase (ERK) pathway inhibition targeting active FGF4 signaling are not affected by mTOR activation. These data indicate a specific role for p38-MAPKs in providing a permissive translational environment during mouse blastocyst PrE differentiation that is distinct from classically reported FGF4-based mechanisms.

Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Embryology Institute of Developmental Biology and Biomedical Sciences Faculty of Biology University of Warsaw Warsaw Poland

Laboratory of Biochemistry and Molecular Biology of Germ Cells Institute of Animal Physiology and Genetics Liběchov Czech Republic

Laboratory of Early Mammalian Developmental Biology Department of Molecular Biology and Genetics Faculty of Science University of South Bohemia České Budějovice Czech Republic

Laboratory of RNA Biochemistry Department of Genetics and Microbiology Faculty of Science Charles University Prague 2 Czech Republic

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