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.

Central European Institute of Technology Masaryk University Kamenice 753 5 62500 Brno Czech Republic

Department of Genetics and Reproduction Central European Institute of Technology Veterinary Research Institute Hudcova 296 70 621 00 Brno Czech Republic

Laboratory of Biochemistry and Molecular Biology of Germ Cells Institute of Animal Physiology and Genetics Czech Academy of Sciences Rumburská 89 27721 Liběchov Czech Republic

Laboratory of Cell Division Control Institute of Animal Physiology and Genetics Czech Academy of Sciences Rumburská 89 27721 Liběchov Czech Republic

Laboratory of Early Mammalian Developmental Biology Department of Molecular Biology and Genetics Faculty of Science University of South Bohemia Branišovská 31 37005 České Budějovice Czech Republic

Laboratory of Functional Genomics and Proteomics National Centre for Biomolecular Research Faculty of Science Masaryk University Kamenice 753 5 62500 Brno Czech Republic

Zobrazit více v PubMed

Chazaud C, Yamanaka Y. 2016. Lineage specification in the mouse preimplantation embryo. Development 143, 1063-1074. (10.1242/dev.128314) PubMed DOI

Plusa B, Piliszek A. 2020. Common principles of early mammalian embryo self-organisation. Development 147, dev183079. (10.1242/dev.183079) PubMed DOI

Vinot S, Le T, Maro B, Louvet-Vallée S. 2004. Two PAR6 proteins become asymmetrically localized during establishment of polarity in mouse oocytes. Curr. Biol. 14, 520-525. (10.1016/j.cub.2004.02.061) PubMed DOI

Vinot S, Le T, Ohno S, Pawson T, Maro B, Louvet-Vallée S. et al. 2005. Asymmetric distribution of PAR proteins in the mouse embryo begins at the 8-cell stage during compaction. Dev. Biol. 282, 307-319. (10.1016/j.ydbio.2005.03.001) PubMed DOI

Louvet S, Aghion J, Santa-Maria A, Mangeat P. Maro B. 1996. Ezrin becomes restricted to outer cells following asymmetrical division in the preimplantation mouse embryo. Dev. Biol. 177, 568-579. (10.1006/dbio.1996.0186) PubMed DOI

Kono K, Tamashiro DA, Alarcon VB. 2014. Inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling in the mouse blastocyst. Dev. Biol. 394, 142-155. (10.1016/j.ydbio.2014.06.023) PubMed DOI PMC

Mihajlovic AI, Bruce AW. 2016. Rho-associated protein kinase regulates subcellular localisation of Angiomotin and Hippo-signalling during preimplantation mouse embryo development. Reprod. Biomed. Online 33, 381-390. (10.1016/j.rbmo.2016.06.028) PubMed DOI

Nishioka N, Yamamoto S, Kiyonari H, Sato H, Sawada A, Ota M, Nakao K, Sasaki H. 2008. Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos. Mech. Dev. 125, 270-283. (10.1016/j.mod.2007.11.002) PubMed DOI

Hirate Y, et al. 2013. Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos. Curr. Biol. 23, 1181-1194. (10.1016/j.cub.2013.05.014) PubMed DOI PMC

Hirate Y, Hirahara S, Inoue K, Kiyonari H, Niwa H, Sasaki H. 2015. Par-aPKC-dependent and -independent mechanisms cooperatively control cell polarity, Hippo signaling, and cell positioning in 16-cell stage mouse embryos. Dev. Growth Differ. 57, 544-556. (10.1111/dgd.12235) PubMed DOI

Wicklow E, Blij S, Frum T, Hirate Y, Lang RA, Sasaki H, Ralston A. 2014. HIPPO pathway members restrict SOX2 to the inner cell mass where it promotes ICM fates in the mouse blastocyst. PLoS Genet. 10, e1004618. (10.1371/journal.pgen.1004618) PubMed DOI PMC

Pedersen RA, Wu K, Balakier H. 1986. Origin of the inner cell mass in mouse embryos: cell lineage analysis by microinjection. Dev. Biol. 117, 581-595. (10.1016/0012-1606(86)90327-1) PubMed DOI

Johnson MH, Ziomek CA. 1981. Induction of polarity in mouse 8-cell blastomeres: specificity, geometry, and stability. J. Cell. Biol. 91, 303-308. (10.1083/jcb.91.1.303) PubMed DOI PMC

Morris SA. 2011. Cell fate in the early mouse embryo: sorting out the influence of developmental history on lineage choice. Reprod. Biomed. Online 22, 521-524. (10.1016/j.rbmo.2011.02.009) PubMed DOI

Anani S, Bhat S, Honma-Yamanaka N, Krawchuk D, Yamanaka Y. 2014. Initiation of Hippo signaling is linked to polarity rather than to cell position in the pre-implantation mouse embryo. Development 141, 2813-2824. (10.1242/dev.107276) PubMed DOI

Samarage CR, White MD, Álvarez YD, Fierro-González JC, Henon Y, Jesudason EC, Bissiere S, Fouras A, Plachta N. 2015. Cortical tension allocates the first inner cells of the mammalian embryo. Dev. Cell 34, 435-447. (10.1016/j.devcel.2015.07.004) PubMed DOI

Watanabe T, Biggins JS, Tannan NB, Srinivas S. 2014. Limited predictive value of blastomere angle of division in trophectoderm and inner cell mass specification. Development 141, 2279-2288. (10.1242/dev.103267) PubMed DOI PMC

Plusa B, Frankenberg S, Chalmers A, Hadjantonakis A-K, Moore CA, Papalopulu N, Papaioannou VE, Glover DM, Zernicka-Goetz M. 2005. Downregulation of Par3 and aPKC function directs cells towards the ICM in the preimplantation mouse embryo. J. Cell Sci. 118, 505-515. (10.1242/jcs.01666) PubMed DOI

Mihajlovic AI, Bruce AW. 2017. The first cell-fate decision of mouse preimplantation embryo development: integrating cell position and polarity. Open Biol. 7, 170210. (10.1098/rsob.170210) PubMed DOI PMC

White MD, Zenker J, Bissiere S, Plachta N. et al. 2018. Instructions for assembling the early mammalian embryo. Dev. Cell 45, 667-679. (10.1016/j.devcel.2018.05.013) PubMed DOI

Korotkevich E, Niwayama R, Courtois A, Friese S, Berger N, Buchholz F, Hiiragi T. 2017. The apical domain is required and sufficient for the first lineage segregation in the mouse embryo. Dev. Cell 40, 235-247.e7. (10.1016/j.devcel.2017.01.006) PubMed DOI PMC

Dard N, Louvet-Vallee S, Maro B. 2009. Orientation of mitotic spindles during the 8- to 16-cell stage transition in mouse embryos. PLoS ONE 4, e8171. (10.1371/journal.pone.0008171) PubMed DOI PMC

Fleming TP. 1987. A quantitative analysis of cell allocation to trophectoderm and inner cell mass in the mouse blastocyst. Dev. Biol. 119, 520-531. (10.1016/0012-1606(87)90055-8) PubMed DOI

Ajduk A, Biswas Shivhare S, Zernicka-Goetz M. 2014. The basal position of nuclei is one pre-requisite for asymmetric cell divisions in the early mouse embryo. Dev. Biol. 392, 133-140. (10.1016/j.ydbio.2014.05.009) PubMed DOI PMC

Humiecka M, Szpila M, Kłoś P, Maleszewski M, Szczepańska K. 2017. Mouse blastomeres acquire ability to divide asymmetrically before compaction. PLoS ONE 12, e0175032. (10.1371/journal.pone.0175032) PubMed DOI PMC

Strumpf D, Mao C-A, Yamanaka Y, Ralston A, Chawengsaksophak K, Beck F, Rossant J. 2005. Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst. Development 132, 2093-2102. (10.1242/dev.01801) PubMed DOI

Ralston A, Rossant J. 2008. Cdx2 acts downstream of cell polarization to cell-autonomously promote trophectoderm fate in the early mouse embryo. Dev. Biol. 313, 614-629. (10.1016/j.ydbio.2007.10.054) PubMed DOI

Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. 2003. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113, 631-642. (10.1016/S0092-8674(03)00393-3) PubMed DOI

Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. 2003. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113, 643-655. (10.1016/S0092-8674(03)00392-1) PubMed DOI

Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. 2003. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 17, 126-140. (10.1101/gad.224503) PubMed DOI PMC

Guo G, Huss M, Tong GQ, Wang C, Li Sun L, Clarke ND, Robson P. 2010. Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. Dev. Cell 18, 675-685. (10.1016/j.devcel.2010.02.012) PubMed DOI

Koutsourakis M, Langeveld A, Patient R, Beddington R, Grosveld F. 1999. The transcription factor GATA6 is essential for early extraembryonic development. Development 126, 723-732. (10.1242/dev.126.9.723) PubMed DOI

Schrode N, Saiz N, Di Talia S, Hadjantonakis A-K. 2014. GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst. Dev. Cell 29, 454-467. (10.1016/j.devcel.2014.04.011) PubMed DOI PMC

Leung CY, Zernicka-Goetz M. 2013. Angiomotin prevents pluripotent lineage differentiation in mouse embryos via Hippo pathway-dependent and -independent mechanisms. Nat. Commun. 4, 2251. (10.1038/ncomms3251) PubMed DOI PMC

Nishioka N, et al. 2009. The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev. Cell 16, 398-410. (10.1016/j.devcel.2009.02.003) PubMed DOI

Zernicka-Goetz M, Morris SA, Bruce AW. 2009. Making a firm decision: multifaceted regulation of cell fate in the early mouse embryo. Nat. Rev. Genet. 10, 467-477. (10.1038/nrg2564) PubMed DOI

Bruce AW, Zernicka-Goetz M. 2010. Developmental control of the early mammalian embryo: competition among heterogeneous cells that biases cell fate. Curr. Opin. Genet. Dev. 20, 485-491. (10.1016/j.gde.2010.05.006) PubMed DOI

Morris SA, Teo RTY, Li H, Robson P, Glover DM, Zernicka-Goetz M. 2010. Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo. Proc. Natl Acad. Sci. USA 107, 6364-6369. (10.1073/pnas.0915063107) PubMed DOI PMC

Yamanaka Y, Lanner F, Rossant J. 2010. FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst. Development 137, 715-724. (10.1242/dev.043471) PubMed DOI

Morris SA, Graham SJL, Jedrusik A, Zernicka-Goetz M. 2013. The differential response to Fgf signalling in cells internalized at different times influences lineage segregation in preimplantation mouse embryos. Open Biol. 3, 130104. (10.1098/rsob.130104) PubMed DOI PMC

Ohnishi Y, et al. 2014. Cell-to-cell expression variability followed by signal reinforcement progressively segregates early mouse lineages. Nat. Cell Biol. 16, 27-37. (10.1038/ncb2881) PubMed DOI PMC

Krupa M, Mazur E, Szczepańska K, Filimonow K, Maleszewski M, Suwińska A. 2014. Allocation of inner cells to epiblast vs primitive endoderm in the mouse embryo is biased but not determined by the round of asymmetric divisions (8–>16- and 16–>32-cells). Dev. Biol. 385, 136-148. (10.1016/j.ydbio.2013.09.008) PubMed DOI

Mihajlovic AI, Thamodaran V, Bruce AW. 2015. The first two cell-fate decisions of preimplantation mouse embryo development are not functionally independent. Sci. Rep. 5, 15034. (10.1038/srep15034) PubMed DOI PMC

Fonseca BD, Smith EM, Yelle N, Alain T, Bushell M, Pause A. 2014. The ever-evolving role of mTOR in translation. Semin. Cell Dev. Biol. 36, 102-112. (10.1016/j.semcdb.2014.09.014) PubMed DOI

Yang M, Lu Y, Piao W, Jin H. 2022. The translational regulation in mTOR pathway. Biomolecules 12, 802. (10.3390/biom12060802) PubMed DOI PMC

Liu GY, Sabatini DM. 2020. mTOR at the nexus of nutrition, growth, ageing and disease. Nat. Rev. Mol. Cell Biol. 21, 183-203. (10.1038/s41580-019-0199-y) PubMed DOI PMC

Saxton RA, Sabatini DM. 2017. mTOR signaling in growth, metabolism, and disease. Cell 168, 960-976. (10.1016/j.cell.2017.02.004) PubMed DOI PMC

Beretta L, Gingras AC, Svitkin YV, Hall MN, Sonenberg N. et al. 1996. Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. EMBO J. 15, 658-664. (10.1002/j.1460-2075.1996.tb00398.x) PubMed DOI PMC

Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM. 2012. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485, 109-113. (10.1038/nature11083) PubMed DOI PMC

Yamashita R, Suzuki Y, Takeuchi N, Wakaguri H, Ueda T, Sugano S, Nakai K. 2008. Comprehensive detection of human terminal oligo-pyrimidine (TOP) genes and analysis of their characteristics. Nucleic Acids Res. 36, 3707-3715. (10.1093/nar/gkn248) PubMed DOI PMC

Yoshihama M, et al. 2002. The human ribosomal protein genes: sequencing and comparative analysis of 73 genes. Genome Res. 12, 379-390. (10.1101/gr.214202) PubMed DOI PMC

Berman AJ, Thoreen CC, Dedeic Z, Chettle J, Roux PP, Blagden SP. 2021. Controversies around the function of LARP1. RNA Biol. 18, 207-217. (10.1080/15476286.2020.1733787) PubMed DOI PMC

Lee SE, Sun S-C, Choi H-Y, Uhm S-J, Kim N-H. 2012. mTOR is required for asymmetric division through small GTPases in mouse oocytes. Mol. Reprod. Dev. 79, 356-366. (10.1002/mrd.22035) PubMed DOI

Susor A, et al. 2015. Temporal and spatial regulation of translation in the mammalian oocyte via the mTOR-eIF4F pathway. Nat. Commun. 6, 6078. (10.1038/ncomms7078) PubMed DOI PMC

Tetkova A, Jansova D, Susor A. 2019. Spatio-temporal expression of ANK2 promotes cytokinesis in oocytes. Sci. Rep. 9, 13121. (10.1038/s41598-019-49483-5) PubMed DOI PMC

Li Y, et al. 2021. Regulation of the mammalian maternal-to-embryonic transition by eukaryotic translation initiation factor 4E. Development 148, dev190793. (10.1242/dev.190793) PubMed DOI PMC

Bulut-Karslioglu A, Biechele S, Jin H, Macrae TA, Hejna M, Gertsenstein M, Song JS, Ramalho-Santos M. 2016. Inhibition of mTOR induces a paused pluripotent state. Nature 540, 119-123. (10.1038/nature20578) PubMed DOI PMC

Thamodaran V, Bruce AW. 2016. p38 (Mapk14/11) occupies a regulatory node governing entry into primitive endoderm differentiation during preimplantation mouse embryo development. Open Biol. 6, 160190. (10.1098/rsob.160190) PubMed DOI PMC

Bora P, Thamodaran V, Šušor A, Bruce AW. 2019. p38-Mitogen activated kinases mediate a developmental regulatory response to amino acid depletion and associated oxidative stress in mouse blastocyst embryos. Front. Cell Dev. Biol. 7, 276. (10.3389/fcell.2019.00276) PubMed DOI PMC

Bora P, et al. 2021. p38-MAPK-mediated translation regulation during early blastocyst development is required for primitive endoderm differentiation in mice. Commun. Biol. 4, 788. (10.1038/s42003-021-02290-z) PubMed DOI PMC

Bowling S, et al. 2018. P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development. Nat. Commun. 9, 1763. (10.1038/s41467-018-04167-y) PubMed DOI PMC

Jansova D, Koncicka M, Tetkova A, Cerna R, Malik R, Del Llano E, Kubelka M, Susor A. 2017. Regulation of 4E-BP1 activity in the mammalian oocyte. Cell Cycle 16, 927-939. (10.1080/15384101.2017.1295178) PubMed DOI PMC

Severance AL, Latham KE. 2017. PLK1 regulates spindle association of phosphorylated eukaryotic translation initiation factor 4E-binding protein and spindle function in mouse oocytes. Am. J. Physiol. Cell Physiol. 313, C501-C515. (10.1152/ajpcell.00075.2017) PubMed DOI PMC

Fukao A, Tomohiro T, Fujiwara T. 2021. Translation initiation regulated by RNA-binding protein in mammals: the modulation of translation initiation complex by trans-acting factors. Cells 10, 1711. (10.3390/cells10071711) PubMed DOI PMC

Moerke NJ, et al. 2007. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell 128, 257-267. (10.1016/j.cell.2006.11.046) PubMed DOI

Vestweber D, Gossler A, Boller K, Kemler R. 1987. Expression and distribution of cell adhesion molecule uvomorulin in mouse preimplantation embryos. Dev. Biol. 124, 451-456. (10.1016/0012-1606(87)90498-2) PubMed DOI

Kovacovicova K, Awadova T, Mikel P, Anger M. et al. 2016. In vitro maturation of mouse oocytes increases the level of Kif11/Eg5 on meiosis II spindles. Biol. Reprod. 95, 18. (10.1095/biolreprod.115.133900) PubMed DOI

Stevens SR, Rasband MN. 2022. Pleiotropic ankyrins: scaffolds for ion channels and transporters. Channels (Austin) 16, 216-229. (10.1080/19336950.2022.2120467) PubMed DOI PMC

Ayalon G, avis JQ, Scotland PB, Bennett V. et al. 2008. An ankyrin-based mechanism for functional organization of dystrophin and dystroglycan. Cell 135, 1189-1200. (10.1016/j.cell.2008.10.018) PubMed DOI

Urnavicius L, Zhang K, Diamant AG, Motz C, Schlager MA, Yu M, Patel NA, Robinson CV, Carter AP. 2015. The structure of the dynactin complex and its interaction with dynein. Science 347, 1441-1446. (10.1126/science.aaa4080) PubMed DOI PMC

Henning D, So RB, Jin R, Lau LF, Valdez BC. 2003. Silencing of RNA helicase II/Gualpha inhibits mammalian ribosomal RNA production. J. Biol. Chem. 278, 52 307-52 314. (10.1074/jbc.M310846200) PubMed DOI

Fuller-Pace FV, Nicol SM. 2012. DEAD-box RNA helicases as transcription cofactors. Methods Enzymol. 511, 347-367. (10.1016/B978-0-12-396546-2.00016-4) PubMed DOI

Posfai E, Petropoulos S, De Barros FRO, Schell JP, Jurisica I, Sandberg R, Lanner F, Rossant J. 2017. Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo. Elife 6, e22906. (10.7554/eLife.22906) PubMed DOI PMC

Allegre N, et al. 2022. NANOG initiates epiblast fate through the coordination of pluripotency genes expression. Nat. Commun. 13, 3550. (10.1038/s41467-022-30858-8) PubMed DOI PMC

Ma S, Meng Z, Chen R, Guan K-L. 2019. The hippo pathway: biology and pathophysiology. Annu. Rev. Biochem. 88, 577-604. (10.1146/annurev-biochem-013118-111829) PubMed DOI

Chazaud C, Yamanaka Y, Pawson T, Rossant J. 2006. Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway. Dev. Cell 10, 615-624. (10.1016/j.devcel.2006.02.020) PubMed DOI

Cockman E, Anderson P, Ivanov P. 2020. TOP mRNPs: molecular mechanisms and principles of regulation. Biomolecules 10, 969. (10.3390/biom10070969) PubMed DOI PMC

Bora P, Gahurova L, Hauserova A, Stiborova M, Collier R, Potěšil D, Zdráhal Z, Bruce AW. 2021. DDX21 is a p38-MAPK-sensitive nucleolar protein necessary for mouse preimplantation embryo development and cell-fate specification. Open Biol. 11, 210092. (10.1098/rsob.210092) PubMed DOI PMC

Kalous J, Jansova D, Susor A. 2020. Role of cyclin-dependent kinase 1 in translational regulation in the M-phase. Cells 9, 1568. (10.3390/cells9071568) PubMed DOI PMC

Masek T, Del Llano E, Gahurova L, Kubelka M, Susor A, Roucova K, Lin C-J, Bruce AW, Pospisek M. 2020. Identifying the translatome of mouse NEBD-stage oocytes via SSP-Profiling; a novel polysome fractionation method. Int. J. Mol. Sci. 21, 1254. (10.3390/ijms21041254) PubMed DOI PMC

Ozadam H, et al. . 2023. Single-cell quantification of ribosome occupancy in early mouse development. Nature 618, 1057-1064. (10.1038/s41586-023-06228-9) PubMed DOI PMC

Muzumdar MD, Tasic B, Miyamichi K, Li L, Luo L. 2007. A global double-fluorescent Cre reporter mouse. Genesis 45, 593-605. (10.1002/dvg.20335) PubMed DOI

Horn T, Boutros M. 2010. E-RNAi: a web application for the multi-species design of RNAi reagents—2010 update. Nucleic Acids Res. 38, W332-W339. (10.1093/nar/gkq317) PubMed DOI PMC

Lemaire P, Garrett N, Gurdon JB. 1995. Expression cloning of Siamois, a Xenopus homeobox gene expressed in dorsal-vegetal cells of blastulae and able to induce a complete secondary axis. Cell 81, 85-94. (10.1016/0092-8674(95)90373-9) PubMed DOI

McGuinness BE, et al. 2009. Regulation of APC/C activity in oocytes by a Bub1-dependent spindle assembly checkpoint. Curr. Biol. 19, 369-380. (10.1016/j.cub.2009.01.064) PubMed DOI

Schindelin J, et al. 2012. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676-682. (10.1038/nmeth.2019) PubMed DOI PMC

Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25, 402-408. (10.1006/meth.2001.1262) PubMed DOI

Gahurova L, et al. . 2023. Spatial positioning of preimplantation mouse embryo cells is regulated by mTORC1 and m7G-cap dependent translation at the 8- to 16-cell transition. Figshare. (10.6084/m9.figshare.c.6760116) PubMed DOI PMC

The translational oscillation in oocyte and early embryo development

Spatial positioning of preimplantation mouse embryo cells is regulated by mTORC1 and m7G-cap-dependent translation at the 8- to 16-cell transition

Zobrazit více v PubMed

figshare
10.6084/m9.figshare.c.6760116