Abstract
One of the unanswered questions in mammalian development is how the embryonic–abembryonic axis of the blastocyst is first established. It is possible that the first cleavage division contributes to this process, because in most mouse embryos the progeny of one two-cell blastomere primarily populate the embryonic part of the blastocyst and the progeny of its sister populate the abembryonic part1,2,3,4. However, it is not known whether the embryonic–abembryonic axis is set up by the first cleavage itself, by polarity in the oocyte that then sets the first cleavage plane with respect to the animal pole, or indeed whether it can be divorced entirely from the first cleavage and established in relation to the animal pole. Here we test the importance of the orientation of the first cleavage by imposing an elongated shape on the zygote so that the division no longer passes close to the animal pole, marked by the second polar body. Non-invasive lineage tracing shows that even when the first cleavage occurs along the short axis imposed by this experimental treatment, the progeny of the resulting two-cell blastomeres tend to populate the respective embryonic and abembryonic parts of the blastocyst. Thus, the first cleavage contributes to breaking the symmetry of the embryo, generating blastomeres with different developmental characteristics.
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Acknowledgements
This work was supported by a Wellcome Trust Senior Research Fellowship to M.Z.-G. and a BBSRC Project Grant to M.Z.-G. and D.M.G. K.P.N. was holding a Marie Curie Fellowship from the European Union. V.E.P. acknowledges support from the NIH. B.P. is on leave from the Department of Experimental Embryology at The Polish Academy of Science, Jastrzebic, Poland.
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Supplementary information
Supplementary Movie S1
Time-lapse image of first cleavage in zygotes expressing H2B-EGFP. The first cleavage in a series of 7 zygotes that divided during time-lapse imaging of 14 embryos. The PB lies within 30° of the plane defined by the metaphase plate position in 6 zygotes. (MOV 3009 kb)
Supplementary Movie S2
Time-lapse DIC/ fluorescence images of zygotes expressing H2B-EGFP and with marked sperm entry site. The sperm entry site was marked with a fluorescent bead as previously described3. (MOV 1250 kb)
Supplementary Movie S3
Time-lapse images of first cleavage division in zygotes in which the animal pole was transplanted to 90° of its original position. The first cleavage in this series of 7 embryos lies within 30° of the new position of the PB in 6 cases. The protocol for transplantation is as previously described8. (MOV 3734 kb)
Supplementary Movie S4 section 2
Time-lapse images of a series of control embryos tracking the path of pronuclei migration. Movie in 5 sections. (MOV 4501 kb)
Supplementary Movie S5 section 2
Time-lapse images of a series of embryos treated for 4 h with 5 g/ml cytochalasin B to depolymerise actin filaments during the time of pronuclei migration. Movie in 6 sections. (MOV 4298 kb)
Supplementary Figure S1
Positions of clones derived from 2-cell blastomeres from experimentally elongated zygotes in relation to blastocyst morphology. (DOC 245 kb)
Supplementary Figure Legend
Legend to accompany the above Supplementary Figure. (DOC 21 kb)
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Plusa, B., Hadjantonakis, AK., Gray, D. et al. The first cleavage of the mouse zygote predicts the blastocyst axis. Nature 434, 391–395 (2005). https://doi.org/10.1038/nature03388
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DOI: https://doi.org/10.1038/nature03388
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