Publication details
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
| Authors | |
|---|---|
| Year of publication | 2023 |
| Type | Article in Periodical |
| Magazine / Source | OPEN BIOLOGY |
| MU Faculty or unit | |
| 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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