Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Cyclin E–Cdk2 temporally regulates centrosome assembly and establishment of polarity in Caenorhabditis elegans embryos

Nature Cell Biology volume 8, pages 1441–1447 (2006)Cite this article

Abstract

Establishment of polarity in C. elegans embryos is dependent on the centrosome1. The sperm contributes a pair of centrioles to the egg and these centrioles remain incapable of polarizing the cortex while the egg completes meiosis. Coincident with the establishment of polarity, the centrioles recruit centrosomal proteins1, several of which are required for polarity1,2,3, suggesting that the temporal regulation of centrosome assembly may control the initiation of polarization. We found that cyclin E–Cdk2 is required for the establishment of polarity. Cyclin E–Cdk2 controls the recruitment of centrosomal proteins specifically at the time of polarity establishment. Cyclin E is required for several examples of asymmetric cell division and fate determination in C. elegans and Drosophila4,5,6. Here, we suggest a possible mechanism for cyclin E–Cdk2-dependent differentiation: the establishment of cortical polarity by the centrosome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Cyclin E–Cdk2 is required for polarity establishment.
Figure 2: Cell-cycle delays associated with depletion of other cyclins do not prevent polarity establishment.
Figure 3: Cyclin E–Cdk2 is required for centrosomal protein recruitment during polarity establishment.
Figure 4: Cyclin E and Cdk2 are mutually required for colocalization around the sperm chromatin/centrioles before polarity establishment, independently of SPD-5 and SPD-2.

Similar content being viewed by others

References

  1. Cowan, C. R. & Hyman, A. A. Centrosomes direct cell polarity independently of microtubule assembly in C. elegans embryos. Nature 431, 92–96 (2004).

    Article  CAS  Google Scholar 

  2. O'Connell, K. F., Maxwell, K. N. & White, J. G. The spd-2 gene is required for polarization of the anteroposterior axis and formation of the sperm asters in the Caenorhabditis elegans zygote. Dev. Biol. 222, 55–70 (2000).

    Article  CAS  Google Scholar 

  3. Hamill, D. R., Severson, A. F., Carter, J. C. & Bowerman, B. Centrosome maturation and mitotic spindle assembly in C. elegans require SPD-5, a protein with multiple coiled-coil domains. Dev. Cell 3, 673–684 (2002).

    Article  CAS  Google Scholar 

  4. Bhat, K. M. & Apsel, N. Upregulation of Mitimere and Nubbin acts through cyclin E to confer self-renewing asymmetric division potential to neural precursor cells. Development 131, 1123–1134 (2004).

    Article  CAS  Google Scholar 

  5. Berger, C., Pallavi, S. K., Prasad, M., Shashidhara, L. S. & Technau, G. M. A critical role for cyclin E in cell fate determination in the central nervous system of Drosophila melanogaster. Nature Cell Biol. 7, 56–62 (2005).

    Article  CAS  Google Scholar 

  6. Fay, D. S. & Han, M. Mutations in cye-1, a Caenorhabditis elegans cyclin E homolog, reveal coordination between cell-cycle control and vulval development. Development 127, 4049–4060 (2000).

    CAS  PubMed  Google Scholar 

  7. Schneider, S. Q. & Bowerman, B. Cell polarity and the cytoskeleton in the Caenorhabditis elegans zygote. Annu. Rev. Genet. 37, 221–249 (2003).

    Article  CAS  Google Scholar 

  8. Cowan, C. R. & Hyman, A. A. Asymmetric cell division in C. elegans: cortical polarity and spindle positioning. Annu. Rev. Cell Dev. Biol. 20, 427–453 (2004).

    Article  CAS  Google Scholar 

  9. Munro, E. M. PAR proteins and the cytoskeleton: a marriage of equals. Curr. Opin. Cell Biol. 18, 86–94 (2006).

    Article  CAS  Google Scholar 

  10. Munro, E., Nance, J. & Priess, J. R. Cortical flows powered by asymmetrical contraction transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo. Dev. Cell 7, 413–424 (2004).

    Article  CAS  Google Scholar 

  11. Hird, S. Cortical actin movements during the first cell cycle of the Caenorhabditis elegans embryo. J. Cell Sci. 109, 525–533 (1996).

    CAS  PubMed  Google Scholar 

  12. Nance, J. PAR proteins and the establishment of cell polarity during C. elegans development. Bioessays 27, 126–135 (2005).

    Article  CAS  Google Scholar 

  13. Piano, F., Schetter, A. J., Mangone, M., Stein, L. & Kemphues, K. J. RNAi analysis of genes expressed in the ovary of Caenorhabditis elegans. Curr. Biol. 10, 1619–1622 (2000).

    Article  CAS  Google Scholar 

  14. Gunsalus, K. C., Yueh, W. C., MacMenamin, P. & Piano, F. RNAiDB and PhenoBlast: web tools for genome-wide phenotypic mapping projects. Nucleic Acids Res. 32, D406–D410 (2004).

    Article  CAS  Google Scholar 

  15. Sonnichsen, B. et al. Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434, 462–469 (2005).

    Article  CAS  Google Scholar 

  16. Zipperlen, P., Fraser, A. G., Kamath, R. S., Martinez-Campos, M. & Ahringer, J. Roles for 147 embryonic lethal genes on C.elegans chromosome I identified by RNA interference and video microscopy. EMBO J. 20, 3984–3992 (2001).

    Article  CAS  Google Scholar 

  17. Seydoux, G., Savage, C. & Greenwald, I. Isolation and characterization of mutations causing abnormal eversion of the vulva in Caenorhabditis elegans. Dev. Biol. 157, 423–436 (1993).

    Article  CAS  Google Scholar 

  18. Brodigan, T. M., Liu, J., Park, M., Kipreos, E. T. & Krause, M. Cyclin E expression during development in Caenorhabditis elegans. Dev. Biol. 254, 102–115 (2003).

    Article  CAS  Google Scholar 

  19. Murray, A. W. Recycling the cell cycle: cyclins revisited. Cell 116, 221–234 (2004).

    Article  CAS  Google Scholar 

  20. Liu, J. & Kipreos, E. T. Evolution of cyclin-dependent kinases (CDKs) and CDK-activating kinases (CAKs): differential conservation of CAKs in yeast and metazoa. Mol. Biol. Evol. 17, 1061–1074 (2000).

    Article  CAS  Google Scholar 

  21. Moroy, T. & Geisen, C. Cyclin E. Int. J .Biochem. Cell. Biol. 36, 1424–1439 (2004).

    Article  CAS  Google Scholar 

  22. Fay, D. S. The cell cycle and development: lessons from C. elegans. Semin. Cell Dev. Biol. 16, 397–406 (2005).

    Article  CAS  Google Scholar 

  23. Koreth, J. & van den Heuvel, S. Cell-cycle control in Caenorhabditis elegans: how the worm moves from G1 to S. Oncogene 24, 2756–2764 (2005).

    Article  CAS  Google Scholar 

  24. Seydoux, G. & Fire, A. Soma-germline asymmetry in the distributions of embryonic RNAs in Caenorhabditis elegans. Development 120, 2823–2834 (1994).

    CAS  PubMed  Google Scholar 

  25. Edgar, L. G., Wolf, N. & Wood, W. B. Early transcription in Caenorhabditis elegans embryos. Development 120, 443–451 (1994).

    CAS  PubMed  Google Scholar 

  26. Sonneville, R. & Gonczy, P. Zyg-11 and cul-2 regulate progression through meiosis II and polarity establishment in C. elegans. Development 131, 3527–3543 (2004).

    Article  CAS  Google Scholar 

  27. Hannak, E., Kirkham, M., Hyman, A. A. & Oegema, K. Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans. J. Cell Biol. 155, 1109–1116 (2001).

    Article  CAS  Google Scholar 

  28. Tilmann, C. & Kimble, J. Cyclin D regulation of a sexually dimorphic asymmetric cell division. Dev. Cell 9, 489–499 (2005).

    Article  CAS  Google Scholar 

  29. Hinchcliffe, E. H. & Sluder, G. Two for two: Cdk2 and its role in centrosome doubling. Oncogene 21, 6154–6160 (2002).

    Article  CAS  Google Scholar 

  30. Tsou, M. F. & Stearns, T. Mechanism limiting centrosome duplication to once per cell cycle. Nature 442, 947–951 (2006).

    Article  CAS  Google Scholar 

  31. Hinchcliffe, E. H., Miller, F. J., Cham, M., Khodjakov, A. & Sluder, G. Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 291, 1547–1550 (2001).

    Article  CAS  Google Scholar 

  32. Balczon, R., Simerly, C., Takahashi, D. & Schatten, G. Arrest of cell cycle progression during first interphase in murine zygotes microinjected with anti-PCM-1 antibodies. Cell Motil. Cytoskeleton 52, 183–192 (2002).

    Article  CAS  Google Scholar 

  33. Cuenca, A. A., Schetter, A., Aceto, D., Kemphues, K. & Seydoux, G. Polarization of the C. elegans zygote proceeds via distinct establishment and maintenance phases. Development 130, 1255–1265 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank: H. Bringmann for advice and discussion; A. Tudor-Constantinescu, C. Hoege, Z. Maliga, L. Pelletier, S. Schonegg and J. Stear for comments on the manuscript; E. Kipreos, J. Kong, K. Oegema, L. Pelletier, A. Pozniakowsky and S. Strome for reagents; and S. Ernst, A. Schwager, A. Zinke for worm bombardment and strain maintenance. Some of the worm strains used in this study are from the C. elegans Genetic Stock Center, funded by the National Institutes of Health (NIH).

Author information

Authors and Affiliations

  1. Max Planck Institute, Molecular Cell Biology & Genetics, Pfotenhauerstrasse 108, Dresden, 01307, Germany

    Carrie R. Cowan & Anthony A. Hyman

Authors
  1. Carrie R. Cowan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anthony A. Hyman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carrie R. Cowan.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Figures S1, S2, S3 and Supplementary Table S1 (PDF 635 kb)

Supplementary Movie 1 (MOV 2288 kb)

Supplementary Movie 2 (MOV 1984 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cowan, C., Hyman, A. Cyclin E–Cdk2 temporally regulates centrosome assembly and establishment of polarity in Caenorhabditis elegans embryos. Nat Cell Biol 8, 1441–1447 (2006). https://doi.org/10.1038/ncb1511

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1511

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing