Nejvíce citovaný článek - PubMed ID 28794108
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 (m7G-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.
- Klíčová slova
- EIF4EBP1/4EBP1, TOP-motif, cell fate, inner cell mass/ICM and cell positioning, mTOR/mTORC1, preimplantation mouse embryo,
- MeSH
- blastocysta * MeSH
- buněčná diferenciace fyziologie MeSH
- buněčný rodokmen MeSH
- embryo savčí * MeSH
- mTORC1 MeSH
- myši MeSH
- savci MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- mTORC1 MeSH
Cells are equipped with a diverse network of signaling and regulatory proteins that function as cell cycle regulators and checkpoint proteins to ensure the proper progression of cell division. A key regulator of cell division is polo-like kinase 1 (PLK1), a member of the serine/threonine kinase family that plays an important role in regulating the mitotic and meiotic cell cycle. The phosphorylation of specific substrates mediated by PLK1 controls nuclear envelope breakdown (NEBD), centrosome maturation, proper spindle assembly, chromosome segregation, and cytokinesis. In mammalian oogenesis, PLK1 is essential for resuming meiosis before ovulation and for establishing the meiotic spindle. Among other potential roles, PLK1 regulates the localized translation of spindle-enriched mRNAs by phosphorylating and thereby inhibiting the translational repressor 4E-BP1, a downstream target of the mTOR (mammalian target of rapamycin) pathway. In this review, we summarize the functions of PLK1 in mitosis, meiosis, and cytokinesis and focus on the role of PLK1 in regulating mRNA translation. However, knowledge of the role of PLK1 in the regulation of meiosis remains limited.
- Klíčová slova
- PLK1, mRNA translation, meiosis, mitosis, oocytes, polo-like kinase 1, spindle,
- MeSH
- lidé MeSH
- meióza MeSH
- mitóza MeSH
- polo-like kinasa 1 MeSH
- protein-serin-threoninkinasy * metabolismus MeSH
- proteiny buněčného cyklu * metabolismus MeSH
- protoonkogenní proteiny metabolismus MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- protein-serin-threoninkinasy * MeSH
- proteiny buněčného cyklu * MeSH
- protoonkogenní proteiny MeSH
In the absence of transcription, the regulation of gene expression in oocytes is controlled almost exclusively at the level of transcriptome and proteome stabilization, and translation. A subset of maternal transcripts is stored in a translationally dormant state in the oocyte, and temporally driven translation of specific mRNAs propel meiotic progression, oocyte-to-embryo transition and early embryo development. We identified Ank2.3 as the only transcript variant present in the mouse oocyte and discovered that it is translated after nuclear envelope breakdown. Here we show that Ank2.3 mRNA is localized in higher concentration in the oocyte nucleoplasm and, after nuclear envelope breakdown, in the newly forming spindle where its translation occurs. Furthermore, we reveal that Ank2.3 mRNA contains an oligo-pyrimidine motif at 5'UTR that predetermines its translation through a cap-dependent pathway. Lastly, we show that prevention of ANK2 translation leads to abnormalities in oocyte cytokinesis.
- MeSH
- ankyriny genetika metabolismus MeSH
- časoprostorová analýza * MeSH
- cytokineze * MeSH
- embryo savčí cytologie fyziologie MeSH
- meióza * MeSH
- messenger RNA genetika metabolismus MeSH
- myši MeSH
- oocyty cytologie fyziologie MeSH
- oogeneze MeSH
- vývojová regulace genové exprese * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Ank2 protein, mouse MeSH Prohlížeč
- ankyriny MeSH
- messenger RNA MeSH
Although the involvement of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in the regulation of cytostatic factor (CSF) activity; as well as in microtubules organization during meiotic maturation of oocytes; has already been described in detail; rather less attention has been paid to the role of ERK1/2 in the regulation of mRNA translation. However; important data on the role of ERK1/2 in translation during oocyte meiosis have been documented. This review focuses on recent findings regarding the regulation of translation and the role of ERK1/2 in this process in the meiotic cycle of mammalian oocytes. The specific role of ERK1/2 in the regulation of mammalian target of rapamycin (mTOR); eukaryotic translation initiation factor 4E (eIF4E) and cytoplasmic polyadenylation element binding protein 1 (CPEB1) activity is addressed along with additional focus on the other key players involved in protein translation.
- Klíčová slova
- CPEB1, ERK1/2, MAP kinase, eIF4E, mTOR, oocyte, translation,
- MeSH
- cytoplazma genetika metabolismus MeSH
- eukaryotický iniciační faktor 4E metabolismus MeSH
- faktory štěpení a polyadenylace mRNA metabolismus MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- lidé MeSH
- meióza * MeSH
- messenger RNA genetika metabolismus MeSH
- mitogenem aktivovaná proteinkinasa 1 metabolismus MeSH
- mitogenem aktivovaná proteinkinasa 3 metabolismus MeSH
- mitogenem aktivované proteinkinasy metabolismus MeSH
- oocyty metabolismus MeSH
- polyadenylace MeSH
- proteosyntéza * MeSH
- signální transdukce MeSH
- TOR serin-threoninkinasy metabolismus MeSH
- vazba proteinů MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- eukaryotický iniciační faktor 4E MeSH
- faktory štěpení a polyadenylace mRNA MeSH
- messenger RNA MeSH
- mitogenem aktivovaná proteinkinasa 1 MeSH
- mitogenem aktivovaná proteinkinasa 3 MeSH
- mitogenem aktivované proteinkinasy MeSH
- TOR serin-threoninkinasy MeSH