| First Author | Gahurova L | Year | 2023 |
| Journal | Open Biol | Volume | 13 |
| Issue | 8 | Pages | 230081 |
| PubMed ID | 37553074 | Mgi Jnum | J:380536 |
| Mgi Id | MGI:8279147 | Doi | 10.1098/rsob.230081 |
| Citation | Gahurova L, et al. (2023) 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 Biol 13(8):230081 |
| abstractText | 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' 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. |
