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First cleavage plane of the mouse egg is not predetermined but defined by the topology of the two apposing pronuclei

Nature volume 430, pages 360–364 (2004)Cite this article

Abstract

Studies of experimentally manipulated embryos1,2,3,4 have led to the long-held conclusion that the polarity of the mouse embryo remains undetermined until the blastocyst stage. However, recent studies5,6,7 reporting that the embryonic–abembryonic axis of the blastocyst arises perpendicular to the first cleavage plane, and hence to the animal–vegetal axis of the zygote, have led to the claim that the axis of the mouse embryo is already specified in the egg. Here we show that there is no specification of the axis in the egg. Time-lapse recordings show that the second polar body does not mark a stationary animal pole, but instead, in half of the embryos, moves towards a first cleavage plane. The first cleavage plane coincides with the plane defined by the two apposing pronuclei once they have moved to the centre of the egg. Pronuclear transfer experiments confirm that the first cleavage plane is not determined in early interphase but rather is specified by the newly formed topology of the two pronuclei. The microtubule networks that allow mixing of parental chromosomes before dividing into two may be involved in these processes.

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Figure 1: The 2pb moves towards the first cleavage plane in half the embryos.
Figure 2: The first cleavage plane is specified by the topology of the two apposing pronuclei in the egg centre.
Figure 3: Relationship between cytoskeleton, chromosomes and first cleavage plane specification.
Figure 4: First cleavage plane is not determined in early interphase but is specified according to the newly formed topology of the pronuclei after manipulation.

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References

  1. Tarkowski, A. K. Experiments on the development of isolated blastomeres of mouse eggs. Nature 184, 1286–1287 (1959)

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Tarkowski, A. K. & Wroblewska, J. Development of blastomeres of mouse eggs isolated at the 4- and 8-cell stage. J. Embryol. Exp. Morphol. 18, 155–180 (1967)

    CAS  PubMed  Google Scholar 

  3. Rossant, J. Postimplantation development of blastomeres isolated from 4- and 8-cell mouse eggs. J. Embryol. Exp. Morphol. 36, 283–290 (1976)

    CAS  PubMed  Google Scholar 

  4. Tarkowski, A. K. Mouse chimaeras developed from fused eggs. Nature 190, 857–860 (1961)

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Gardner, R. L. The early blastocyst is bilaterally symmetrical and its axis of symmetry is aligned with the animal–vegetal axis of the zygote in the mouse. Development 124, 289–301 (1997)

    CAS  PubMed  Google Scholar 

  6. Gardner, R. L. Specification of embryonic axes begins before cleavage in normal mouse development. Development 128, 839–847 (2001)

    CAS  PubMed  Google Scholar 

  7. Piotrowska, K., Wianny, F., Pedersen, R. A. & Zernicka-Goetz, M. Blastomeres arising from the first cleavage division have distinguishable fates in normal mouse development. Development 128, 3739–3748 (2001)

    CAS  PubMed  Google Scholar 

  8. Piotrowska, K. & Zernicka-Goetz, M. Role for sperm in spatial patterning of the early mouse embryo. Nature 409, 517–521 (2001)

    Article  ADS  CAS  PubMed  Google Scholar 

  9. Plusa, B., Grabarek, J. B., Piotrowska, K., Glover, D. M. & Zernicka-Goetz, M. Site of the previous meiotic division defines cleavage orientation in the mouse embryo. Nature Cell Biol. 4, 811–815 (2002)

    Article  CAS  PubMed  Google Scholar 

  10. Schatten, G., Simerly, C. & Schatten, H. Microtubule configurations during fertilization, mitosis, and early development in the mouse and the requirement for egg microtubule-mediated motility during mammalian fertilization. Proc. Natl Acad. Sci. USA 82, 4152–4156 (1985)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Maro, B., Johnson, M. H., Webb, M. & Flach, G. Mechanism of polar body formation in the mouse oocyte: an interaction between the chromosomes, the cytoskeleton and the plasma membrane. J. Embryol. Exp. Morphol. 92, 11–32 (1986)

    CAS  PubMed  Google Scholar 

  12. Maro, B., Howlett, S. K. & Webb, M. Non-spindle microtubule organizing centers in metaphase II-arrested mouse oocytes. J. Cell Biol. 101, 1665–1672 (1985)

    Article  CAS  PubMed  Google Scholar 

  13. Schatten, H., Schatten, G., Mazia, D., Balczon, R. & Simerly, C. Behavior of centrosomes during fertilization and cell division in mouse oocytes and in sea urchin eggs. Proc. Natl Acad. Sci. USA 83, 105–109 (1986)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  14. Canman, J. C. et al. Determining the position of the cell division plane. Nature 424, 1074–1078 (2003)

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Piotrowska, K. & Zernicka-Goetz, M. Early patterning of the mouse embryo–contributions of sperm and egg. Development 129, 5803–5813 (2002)

    Article  CAS  PubMed  Google Scholar 

  16. Johnson, M. H., Eager, D., Muggleton-Harris, A. & Grave, H. M. Mosaicism in organisation concanavalin A receptors on surface membrane of mouse egg. Nature 257, 321–322 (1975)

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Mayer, W., Smith, A., Fundele, R. & Haaf, T. Spatial separation of parental genomes in preimplantation mouse embryos. J. Cell Biol. 148, 629–634 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Paweletz, N., Mazia, D. & Finze, E. M. Fine structural studies of the bipolarization of the mitotic apparatus in the fertilized sea urchin egg. II. Bipolarization before the first mitosis. Eur. J. Cell Biol. 44, 205–213 (1987)

    CAS  PubMed  Google Scholar 

  19. Schatten, G. Sperm incorporation, the pronuclear migrations, and their relation to the establishment of the first embryonic axis: time-lapse video microscopy of the movements during fertilization of the sea urchin Lytechinus variegatus. Dev. Biol. 86, 426–437 (1981)

    Article  CAS  PubMed  Google Scholar 

  20. Zamboni, L., Chakraborty, J. & Smith, D. M. First cleavage division of the mouse zygote. An ultrastructural study. Biol. Reprod. 7, 170–193 (1972)

    Article  CAS  PubMed  Google Scholar 

  21. Heald, R. et al. Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature 382, 420–425 (1996)

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Carazo-Salas, R. E. & Karsenti, E. Long-range communication between chromatin and microtubules in Xenopus egg extracts. Curr. Biol. 13, 1728–1733 (2003)

    Article  CAS  PubMed  Google Scholar 

  23. Alarcon, V. B. & Marikawa, Y. Deviation of the blastocyst axis from the first cleavage plane does not affect the quality of mouse postimplantation development. Biol. Reprod. 69, 1208–1212 (2003)

    Article  CAS  PubMed  Google Scholar 

  24. Ho, Y., Wigglesworth, K., Eppig, J. J. & Schultz, R. M. Preimplantation development of mouse embryos in KSOM: augmentation by amino acids and analysis of gene expression. Mol. Reprod. Dev. 41, 232–238 (1995)

    Article  CAS  PubMed  Google Scholar 

  25. McGrath, J. & Solter, D. Nuclear transplantation in the mouse embryo by microsurgery and cell fusion. Science 220, 1300–1302 (1983)

    Article  ADS  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Y. Kaneda for HVJ; Z. Polanski, N. Bobola, A. Tomilin, P. Nielsen, R. Cassada and M. Hoffman for discussions and reading of the manuscript.

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Authors and Affiliations

  1. Max-Planck Institute of Immunobiology, D-79108, Freiburg, Germany

    Takashi Hiiragi & Davor Solter

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  1. Takashi Hiiragi
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Correspondence to Takashi Hiiragi.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Movie 1

This movie shows a time-lapse recording of the embryos developing from zygote to 2-cell. The time-lapse corresponds to the sequential pictures of Fig.1b, covering a period of 7.5 hours. (MOV 1582 kb)

Supplementary Movie 2

This movie shows a time-lapse recording of the embryos developing from zygote to 2-cell. The time-lapse corresponds to the sequential pictures of Fig.1c, covering a period of 7.5 hours. (MOV 1155 kb)

Supplementary Movie 3

This movie shows a time-lapse recording of the embryo developing from zygote to 2-cell. The time-lapse corresponds to the sequential pictures of Fig.2a, covering a period of 17 hours. (MOV 2650 kb)

Supplementary Movie 4

This movie shows a time-lapse recording of the embryos developing from zygote to 2-cell. The time-lapse corresponds to the sequential pictures of Fig.2b, covering a period of 18 hours. (MOV 3305 kb)

Supplementary Movie 5

This movie shows a time-lapse recording of the embryos developing from zygote to 2-cell. The time-lapse corresponds to the sequential pictures of Fig.2c, covering a period of 19 hours. (MOV 4512 kb)

Supplementary Movie 6

This movie shows a time-lapse recording of the embryos developing from zygote to 2-cell following transfer of female pronucleus into fertilized egg from which male pronucleus was removed. Female pronucleus was placed in the pole opposite from 2pb. The time-lapse corresponds to the sequential pictures of Fig.4e, covering a period of 10 hours. (MOV 1967 kb)

Supplementary Methods

Describes the methods for pronuclear transfer and immunofluorescence staining. (DOC 20 kb)

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Hiiragi, T., Solter, D. First cleavage plane of the mouse egg is not predetermined but defined by the topology of the two apposing pronuclei. Nature 430, 360–364 (2004). https://doi.org/10.1038/nature02595

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