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

0543951 - ÚŽFG 2022 RIV GB eng J - Článek v odborném periodiku
Bora, P. - Gahurová, Lenka - Mašek, T. - Hauserová, A. - Potěšil, D. - Jansová, Denisa - Šušor, Andrej - Zdráhal, Z. - Ajduk, A. - Pospíšek, M. - Bruce, A. W.
p38-MAPK-mediated translation regulation during early blastocyst development is required for primitive endoderm differentiation in mice.
Communications Biology. Roč. 4, č. 1 (2021), č. článku 788. E-ISSN 2399-3642
Institucionální podpora: RVO:67985904
Klíčová slova: early blastocyst development * mouse
Obor OECD: Developmental biology
Impakt faktor: 6.548, rok: 2021
Způsob publikování: Open access
https://www.nature.com/articles/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. 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.
Trvalý link: http://hdl.handle.net/11104/0321040