Spatial positioning of preimplantation mouse embryo blastomeres is regulated by mTORC1 and 7mG-cap dependent translation at the 8- to 16-cell transition
Rattachement africain : us, cz. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
ABSTRACT Preimplantation stages of mouse embryo development involve temporal and spatial specification and segregation of three late blastocyst cell lineages; trophectoderm (TE), primitive endoderm (PrE) and epiblast (EPI). Spatial separation of the outer TE lineage from the two inner cell mass (ICM) lineages (PrE and EPI) starts with the 8- to 16-cell transition and concludes following transit through the 16- to 32-cell stages. This results in an early blastocyst ICM derived from descendants of primary founding inner cells and a secondarily contributed population, of which subsequent relative EPI versus PrE potencies are subject to debate. Here, we report generation of primary but not the secondary ICM populations is highly dependent on temporally discreet activation of the mammalian target of Rapamycin (mTOR – specifically mTORC1) during M-phase entry at the 8-cell stage. This role is mediated via regulation of the 7-methylguanosine-(7mG) cap binding initiation complex (EIF4F), linked to translation of a subset of key mRNAs containing 5’ UTR terminal oligopyrimidine (TOP-) or TOP-like sequence motifs; as knockdown of identified TOP-like motif containing transcripts also impairs generation of 16-cell stage primary ICM founders. However, mTOR inhibition induced ICM cell number deficits at the early blastocyst stage can be compensated by the late blastocyst stage, in the absence of inhibition. This compensation is likely initiated at the 32-cell stage when supernumerary outer cells in mTOR-inhibited embryos exhibit molecular characteristics of inner cells. Collectively, the data identify a novel mechanism specifically governing initial spatial segregation of blastomeres in the mouse embryo, that is distinct from those directing subsequent inner cell formation and contributes to germane segregation of late blastocyst lineages.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Spatial positioning of preimplantation mouse embryo blastomeres is regulated by mTORC1 and 7mG-cap dependent translation at the 8- to 16-cell transition
- Date Crossref
- 07/03/2023
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Sewanee: The University of the South pays non établi dans la noticeUniversité ou école supérieure
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University of South Bohemia in České Budějovice pays non établi dans la noticeUniversité ou école supérieure
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Czech Academy of Sciences pays non établi dans la noticeStructure de recherche
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University of Massachusetts Chan Medical School Department of Biochemistry and Molecular Biotechnology pays non établi dans la noticeUniversité ou école supérieure
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Central European Institute of Technology Department of Genetics and Reproduction pays non établi dans la noticeUniversité ou école supérieure
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Veterinary Research Institute pays non établi dans la noticeStructure de recherche
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Masaryk University Central European Institute of Technology pays non établi dans la noticeUniversité ou école supérieure
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Central European Institute of Technology – Masaryk University pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Biochemistry and Molecular Biology of Germ Cells pays non établi dans la noticeStructure de recherche
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Faculty of Science Laboratory of Early Mammalian Developmental Biology (LEMDB) pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Cell Division Control pays non établi dans la noticeStructure de recherche
Sewanee: The University of the South, University of South Bohemia in České Budějovice et Czech Academy of Sciences, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.