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:

Sequential functioning of the ECT-2 RhoGEF, RHO-1 and CDC-42 establishes cell polarity in Caenorhabditis elegans embryos

Abstract

During development, the establishment of cell polarity is important for cells to undergo asymmetric cell divisions that give rise to diverse cell types. In C. elegans embryos, cues from the centrosome trigger the cortical flow of an actomyosin network, leading to the formation of anterior–posterior polarity1. However, its precise mechanism is poorly understood. Here, we show that small GTPases have sequential and crucial functions in this process. ECT-2, a potential guanine nucleotide-exchange factor (GEF)2 for RHO-1, was uniformly distributed at the cortex before polarization, but was excluded from the posterior cortex by the polarity cue from the centrosomes. This local exclusion of ECT-2 led to an asymmetric RHO-1 distribution, which generated a cortical flow of the actomyosin that translocated PAR proteins3 and CDC-42 (Refs 4, 5) to the anterior cortex. Polarized CDC-42 was, in turn, involved in maintaining the established anterior-cortical domains. Our results suggest that a local change in the function of ECT-2 and RHO-1 links the centrosomal polarity cue with the polarization of the cell cortex.

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

Access options

Buy this article

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

Figure 1: CDC-42, RHO-1 and ECT-2 are required for asymmetric spindle positioning in the one-cell embryo.
Figure 2: RHO-1 and CDC-42 have distinct roles in anterior–posterior polarization.
Figure 3: The centrosome mediates exclusion of cortical ECT-2.
Figure 4: Asymmetric distribution of cortical foci of RHO-1 and CDC-42.
Figure 5: A schematic representation of a model for the establishment of anterior–posterior polarity in the C. elegans one-cell embryo.

Similar content being viewed by others

References

  1. 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 

  2. Morita, K., Hirono, K. & Han, M. The Caenorhabditis elegans ect-2 RhoGEF gene regulates cytokinesis and migration of epidermal P cells. EMBO Rep. 6, 1163–1168 (2005).

    Article  CAS  Google Scholar 

  3. Kemphues, K. PARsing embryonic polarity. Cell 12, 345–348 (2000).

    Article  Google Scholar 

  4. Gotta, M., Abraham, M. C. & Ahringer, J. CDC-42 controls early cell polarity and spindle orientation in C. elegans. Curr. Biol. 11, 482–488 (2001).

    Article  CAS  Google Scholar 

  5. Kay, A. J. & Hunter, C. P. CDC-42 regulates PAR protein localization and function to control cellular and embryonic polarity in C. elegans. Curr. Biol. 11, 474–481 (2001).

    Article  CAS  Google Scholar 

  6. 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 

  7. 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 

  8. Wallenfang, M. R. & Seydoux, G. Polarization of the anterior-posterior axis of C. elegans is a microtubule-directed process. Nature 408, 89–92 (2000).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Guo, S. & Kemphues, K. J. A non-muscle myosin required for embryonic polarity in Caenorhabditis elegans. Nature 382, 455–458 (1996).

    Article  CAS  Google Scholar 

  11. Hill, D. P. & Strome, S. An analysis of the role of microfilaments in the establishment and maintenance of asymmetry in Caenorhabditis elegans zygotes. Dev. Biol. 125, 75–84 (1988).

    Article  CAS  Google Scholar 

  12. Shelton, C. A., Carter, J. C., Ellis, G. C. & Bowerman, B. The nonmuscle myosin regulatory light chain gene mlc-4 is required for cytokinesis, anterior-posterior polarity, and body morphology during Caenorhabditis elegans embryogenesis. J. Cell Biol. 146, 439–451 (1999).

    Article  CAS  Google Scholar 

  13. Severson, A. F. & Bowerman, B. Myosin and the PAR proteins polarize microfilament-dependent forces that shape and position mitotic spindles in Caenorhabditis elegans. J. Cell Biol. 161, 21–26 (2003).

    Article  CAS  Google Scholar 

  14. Hall, A. Rho GTPases and the actin cytoskeleton. Science 279, 509–514 (1998).

    Article  CAS  Google Scholar 

  15. Motegi, F., Velarde, N. V., Piano, F. & Sugimoto, A. Two phases of astral microtubule activity during cytokinesis in C. elegans embryos. Dev. Cell 10, 509–520 (2006).

    Article  CAS  Google Scholar 

  16. Jantsch-Plunger, V. et al. CYK-4: A Rho family GTPase activating protein (GAP) required for central spindle formation and cytokinesis. J. Cell Biol. 149, 1391–1404 (2000).

    Article  CAS  Google Scholar 

  17. Dechant, R. & Glotzer, M. Centrosome separation and central spindle assembly act in redundant pathways that regulate microtubule density and trigger cleavage furrow formation. Dev. Cell 4, 333–344 (2003).

    Article  CAS  Google Scholar 

  18. Audhya, A. et al. A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis elegans. J. Cell Biol. 171, 267–279 (2005).

    Article  CAS  Google Scholar 

  19. 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 

  20. Nishimura, Y. & Yonemura, S. Centralspindlin regulates ECT2 and RhoA accumulation at the equatorial cortex during cytokinesis. J. Cell Sci. 119, 104–114 (2006).

    Article  CAS  Google Scholar 

  21. Yuce, O., Piekny, A. & Glotzer, M. An ECT2-centralspindlin complex regulates the localization and function of RhoA. J. Cell Biol. 170, 571–582 (2005).

    Article  Google Scholar 

  22. Hird, S. N. & White, J. G. Cortical and cytoplasmic flow polarity in early embryonic cells of Caenorhabditis elegans. J. Cell Biol. 121, 1343–1355 (1993).

    Article  CAS  Google Scholar 

  23. Etienne-Manneville, S. Cdc42 — the centre of polarity. J. Cell Sci. 117, 1291–1300 (2004).

    Article  CAS  Google Scholar 

  24. Joberty, G., Petersen, C., Gao, L. & Macara, I. G. The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nature Cell Biol. 2, 531–539 (2000).

    Article  CAS  Google Scholar 

  25. Praitis, V., Casey, E., Collar, D. & Austin, J. Creation of low-copy integrated transgenic lines in Caenorhabditis elegans. Genetics 157, 1217–1226 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Maeda, I., Kohara, Y., Yamamoto, M. & Sugimoto, A. Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Curr. Biol. 11, 171–176 (2001).

    Article  CAS  Google Scholar 

  27. Sumiyoshi, E., Sugimoto, A. & Yamamoto, M. Protein phosphatase 4 is required for centrosome maturation in mitosis and sperm meiosis in C. elegans. J. Cell Sci. 115, 1403–1410 (2002).

    CAS  PubMed  Google Scholar 

  28. Edger, L. G. Blastmere culture and analysis. Methods Cell Biol. 48, 303–321 (1995).

    Article  Google Scholar 

Download references

Acknowledgements

We thank N.V. Velarde and F. Piano for kindly providing the strain expressing GFP–moe and for sharing information before publication; F. Matsuzaki for suggestions and thoughtful comments on the manuscript; and G. Seydoux, D. Kiehart, K. Kemphues, A. Audhya and Y. Kohara for their generous gifts of reagents. We also thank Y. Kodama for the initial characterization of the ect-2 gene and all members of our laboratories for helpful discussions. Some of the worm strains used in this study were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health (NIH) National Center for Research Resources. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas 'Systems Genomics' (A.S.) and a Grant-in-Aid for Young Scientists B (F.M.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. F.M. was supported by the Special Postdoctoral Researchers Program of RIKEN.

Author information

Authors and Affiliations

Authors

Contributions

F.M. designed and performed the experiments. F.M. and A.S. performed the data analysis and wrote the paper. A.S. was responsible for project planning and guidance.

Corresponding author

Correspondence to Asako Sugimoto.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Motegi, F., Sugimoto, A. Sequential functioning of the ECT-2 RhoGEF, RHO-1 and CDC-42 establishes cell polarity in Caenorhabditis elegans embryos. Nat Cell Biol 8, 978–985 (2006). https://doi.org/10.1038/ncb1459

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1459

This article is cited by

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