p38-MAPK-mediated translation regulation during early blastocyst development is required for primitive endoderm differentiation in mice

• DOI: 10.1038/s42003-021-02290-z
• Publication Date: 2021-06-25T10:03:07Z
• Authors: Pablo Bora; Lenka Gahurova; Tomáš Mašek; Andrea Hauserova; David Potěšil; Denisa Jansova; Andrej Susor; Zbyněk Zdráhal; Anna Ajduk; Martin Pospíšek; Alexander W. Bruce
• Keywords: Epiblast

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