Spatial positioning of preimplantation mouse embryo cells is regulated by mTORC1 and m(7)G-cap-dependent translation at the 8-to 16-cell transition

0574409 - ÚŽFG 2024 RIV GB eng J - Journal Article
Gahurová, Lenka - Tománková, J. - Černá, P. - Bora, P. - Kubíčková, M. - Virnicchi, G. - Kovačovicová, Kristina - Potěšil, D. - Hruška, P. - Zdráhal, Z. - Anger, Martin - Šušor, Andrej - Bruce, A. W.
Spatial positioning of preimplantation mouse embryo cells is regulated by mTORC1 and m(7)G-cap-dependent translation at the 8-to 16-cell transition.
Open Biology. Roč. 13, č. 8 (2023), č. článku 230081. E-ISSN 2046-2441
Institutional support: RVO:67985904
Keywords : mTOR/mTORC1 * EIF4EBP1/4EBP1 * TOP-motif
OECD category: Developmental biology
Impact factor: 5.8, year: 2022
Method of publishing: Open access
https://royalsocietypublishing.org/doi/10.1098/rsob.230081

Preimplantation mouse embryo development involves temporal-spatial specification and segregation of three blastocyst cell lineages: trophectoderm, primitive endoderm and epiblast. Spatial separation of the outer-trophectoderm lineage from the two other inner-cell-mass (ICM) lineages starts with the 8- to 16-cell transition and concludes at the 32-cell stages. Accordingly, the ICM is derived from primary and secondary contributed cells, with debated relative EPI versus PrE potencies. We report generation of primary but not secondary ICM populations is highly dependent on temporal activation of mammalian target of Rapamycin (mTOR) during 8-cell stage M-phase entry, mediated via regulation of the 7-methylguanosine-cap (m(7)G-cap)-binding initiation complex (EIF4F) and linked to translation of mRNAs containing 5 & PRIME, UTR terminal oligopyrimidine (TOP-) sequence motifs, as knockdown of identified TOP-like motif transcripts impairs generation of primary ICM founders. However, mTOR inhibition-induced ICM cell number deficits in early blastocysts can be compensated by the late blastocyst stage, after inhibitor withdrawal, compensation likely initiated at the 32-cell stage when supernumerary outer cells exhibit molecular characteristics of inner cells. These data identify a novel mechanism specifically governing initial spatial segregation of mouse embryo blastomeres, that is distinct from those directing subsequent inner cell formation, contributing to germane segregation of late blastocyst lineages.
Permanent Link: https://hdl.handle.net/11104/0344736