p38-MAPK-mediated translation regulation during early blastocyst development is required for primitive endoderm differentiation in mice
| Authors | |
|---|---|
| Year of publication | 2021 |
| Type | Article in Periodical |
| Magazine / Source | Communications Biology |
| MU Faculty or unit | |
| Citation | |
| Web | fulltext |
| Doi | http://dx.doi.org/10.1038/s42003-021-02290-z |
| Keywords | ACTIVATED PROTEIN-KINASE; INNER CELL MASS; MAP KINASE; PREIMPLANTATION EMBRYO; MESSENGER-RNA; NA/K-ATPASE; 1A MYBBP1A; P38 MAPK; MOUSE; GROWTH |
| Description | 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. Bora et al. show that an early blastocyst window of p38-MAPK activity regulates ribosome-related gene expression, rRNA precursor processing, polysome formation, and protein translation. This study suggests a distinct role of p38-MAPKs for providing a permissive translational environment during mouse blastocyst primitive endoderm differentiation. |
| Related projects: |