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@article{2305479,
author = {Gahurová, Lenka and Tománková, Jana and Černá, Pavla and Bora, Pablo and Kubíčková, Michaela and Virnicchi, Giorgio and Kovařovicová, Kristina and Potěšil, David and Hruška, Pavel and Zdráhal, Zbyněk and Anger, Martin and Šušot, Andrej and Bruce, Alexander W.},
article_location = {ENGLAND},
article_number = {8},
doi = {http://dx.doi.org/10.1098/rsob.230081},
keywords = {mTOR;mTORC1;EIF4EBP1;4EBP1;TOP-motif;preimplantation mouse embryo;cell fate;inner cell mass;ICM and cell positioning},
language = {eng},
issn = {2046-2441},
journal = {OPEN BIOLOGY},
title = {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},
url = {https://royalsocietypublishing.org/doi/epdf/10.1098/rsob.230081},
volume = {13},
year = {2023}
}
TY - JOUR
ID - 2305479
AU - Gahurová, Lenka - Tománková, Jana - Černá, Pavla - Bora, Pablo - Kubíčková, Michaela - Virnicchi, Giorgio - Kovařovicová, Kristina - Potěšil, David - Hruška, Pavel - Zdráhal, Zbyněk - Anger, Martin - Šušot, Andrej - Bruce, Alexander W.
PY - 2023
TI - 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
JF - OPEN BIOLOGY
VL - 13
IS - 8
SP - 1-19
EP - 1-19
PB - ROYAL SOC
SN - 20462441
KW - mTOR;mTORC1;EIF4EBP1;4EBP1;TOP-motif;preimplantation mouse embryo;cell fate;inner cell mass;ICM and cell positioning
UR - https://royalsocietypublishing.org/doi/epdf/10.1098/rsob.230081
N2 - 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.
ER -
GAHUROVÁ, Lenka, Jana TOMÁNKOVÁ, Pavla ČERNÁ, Pablo BORA, Michaela KUBÍČKOVÁ, Giorgio VIRNICCHI, Kristina KOVAŘOVICOVÁ, David POTĚŠIL, Pavel HRUŠKA, Zbyněk ZDRÁHAL, Martin ANGER, Andrej ŠUŠOT and Alexander W. BRUCE. 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. \textit{OPEN BIOLOGY}. ENGLAND: ROYAL SOC, 2023, vol.~13, No~8, p.~1-19. ISSN~2046-2441. Available from: https://dx.doi.org/10.1098/rsob.230081.
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