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

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Authors	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.
Year of publication	2023
Type	Article in Periodical
Magazine / Source	OPEN BIOLOGY
MU Faculty or unit	Central European Institute of Technology
Citation
Web	fulltext
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
Description	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.
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