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

Commun Biol. 2021 Jun 25;4(1):788. doi: 10.1038/s42003-021-02290-z.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / physiology*
  • Cell Differentiation
  • Cell Lineage
  • DNA-Binding Proteins / physiology
  • Embryonic Development
  • Endoderm / cytology*
  • Mice
  • Protein Biosynthesis*
  • RNA-Binding Proteins / physiology
  • TOR Serine-Threonine Kinases / physiology
  • Transcription Factors / physiology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / physiology*


  • DNA-Binding Proteins
  • Mybbp1a protein, mouse
  • RNA-Binding Proteins
  • Transcription Factors
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases