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:

An unconventional myosin in Drosophila reverses the default handedness in visceral organs

Nature volume 440, pages 798–802 (2006)Cite this article

Abstract

The internal organs of animals often have left–right asymmetry1,2. Although the formation of the anterior–posterior and dorsal–ventral axes in Drosophila is well understood, left–right asymmetry has not been extensively studied. Here we find that the handedness of the embryonic gut and the adult gut and testes is reversed (not randomized) in viable and fertile homozygous Myo31DF mutants. Myo31DF encodes an unconventional myosin, Drosophila MyoIA (also referred to as MyoID in mammals; refs 3, 4), and is the first actin-based motor protein to be implicated in left–right patterning. We find that Myo31DF is required in the hindgut epithelium for normal embryonic handedness. Disruption of actin filaments in the hindgut epithelium randomizes the handedness of the embryonic gut, suggesting that Myo31DF function requires the actin cytoskeleton. Consistent with this, we find that Myo31DF colocalizes with the cytoskeleton. Overexpression of Myo61F, another myosin I (ref. 4), reverses the handedness of the embryonic gut, and its knockdown also causes a left–right patterning defect. These two unconventional myosin I proteins may have antagonistic functions in left–right patterning. We suggest that the actin cytoskeleton and myosin I proteins may be crucial for generating left–right asymmetry in invertebrates.

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: Myo31DF mutation inverses the handedness of embryonic and adult visceral organs.
Figure 2: Embryonic expression of Myo31DF and the subcellular localization of Myo31DF.
Figure 3: Myo31DF is dependent on the actin cytoskeleton to develop left–right asymmetry.

Similar content being viewed by others

References

  1. Wood, W. B. Left–right asymmetry in animal development. Annu. Rev. Cell Dev. Biol. 13, 53–82 (1997)

    Article  CAS  Google Scholar 

  2. Mercola, M. & Levin, M. Left–right asymmetry determination in vertebrates. Annu. Rev. Cell Dev. Biol. 17, 779–805 (2001)

    Article  CAS  Google Scholar 

  3. Gillespie, P. G. et al. Myosin-I nomenclature. J. Cell Biol. 155, 703–704 (2001)

    Article  CAS  Google Scholar 

  4. Morgan, N. S., Heintzelman, M. B. & Mooseker, M. S. Characterization of Myosin-IA and Myosin-IB, two unconventional myosins associated with the Drosophila brush border cytoskeleton. Dev. Biol. 172, 51–71 (1995)

    Article  CAS  Google Scholar 

  5. Hayashi, T. & Murakami, R. Left–right asymmetry in Drosophila melanogaster gut development. Dev. Growth Differ. 43, 239–246 (2001)

    Article  CAS  Google Scholar 

  6. Ligoxygakis, P., Strigini, M. & Averof, M. Specification of left–right asymmetry in the embryonic gut of Drosophila. Development 128, 1171–1174 (2001)

    CAS  PubMed  Google Scholar 

  7. Hayashi, M. et al. Left–right asymmetry in the alimentary canal of the Drosophila embryo. Dev. Growth Differ. 47, 457–460 (2005)

    Article  Google Scholar 

  8. Pascual, A., Huang, K, Neven, J. & Préat, T. Neuroanatomy: Brain asymmetry and long-term memory. Nature 427, 605–606 (2004)

    Article  ADS  CAS  Google Scholar 

  9. Adam, G., Perrimon, N. & Noselli, S. The retinoic-like juvenile hormone controls the looping of left–right asymmetric organs in Drosophila. Development 130, 2397–2406 (2003)

    Article  CAS  Google Scholar 

  10. Spéder, P., Ádám, G. & Noselli, S. Type ID unconventional myosin controls left–right asymmetry in Drosophila. Nature doi:10.1038/nature04623 (this issue)

  11. Iwaki, D. D. & Lengyel, J. A. A Delta–Notch signaling border regulated by Engrailed/Inverted repression specifies boundary cells in the Drosophila hindgut. Mech. Dev. 114, 71–84 (2002)

    Article  CAS  Google Scholar 

  12. Wodarz, A., Hinz, U., Engelbert, M. & Knust, E. Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell 82, 67–76 (1995)

    Article  CAS  Google Scholar 

  13. Edwards, K. A., Demsky, M., Montague, R. A., Weymouth, N. & Kiehart, D. P. GFP–moesin illuminates actin cytoskeleton dynamics in living tissue and demonstrates cell shape change during morphogenesis in Drosophila. Dev. Biol. 191, 103–117 (1997)

    Article  CAS  Google Scholar 

  14. McGuire, S. E. et al. Spatiotemporal rescue of memory dysfunction in Drosophila. Science 302, 1765–1768 (2003)

    Article  ADS  CAS  Google Scholar 

  15. Etienne-Manneville, S. & Hall, A. Rho GTPases in cell biology. Nature 420, 629–635 (2002)

    Article  ADS  CAS  Google Scholar 

  16. Iwaki, D. D., Johansen, K. A., Singer, J. B. & Lengyel, J. A. drumstick, bowl, and lines are required for patterning and cell rearrangement in the Drosophila embryonic hindgut. Dev. Biol. 240, 611–626 (2001)

    Article  CAS  Google Scholar 

  17. Gillespie, P. G., Wagner, M. C. & Hudspeth, A. J. Identification of a 120 kd hair-bundle myosin located near stereociliary tips. Neuron 11, 581–594 (1993)

    Article  CAS  Google Scholar 

  18. Shibazaki, Y., Shimizu, M. & Kuroda, R. Body handedness is directed by genetically determined cytoskeletal dynamics in the early embryo. Curr. Biol. 14, 1462–1467 (2004)

    Article  CAS  Google Scholar 

  19. Huber, L. A. et al. Both calmodulin and unconventional myosin Myr4 regulate membrane trafficking along the recycling pathway of MDCK cells. Traffic 1, 494–503 (2000)

    Article  CAS  Google Scholar 

  20. Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993)

    CAS  Google Scholar 

  21. Martin-Bermudo, M. D., Dunin-Borkowski, O. M. & Brown, N. B. Specificity of PS integrin function during embryogenesis resides in the α subunit extracellular domain. EMBO J. 16, 4184–4193 (1997)

    Article  CAS  Google Scholar 

  22. Tracey, W. D. Jr, Ning, X., Klingler, M., Kramer, S. G. & Gergen, J. P. Quantitative analysis of gene function in the Drosophila embryo. Genetics 154, 273–284 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Strutt, D. I., Weber, U. & Mlodzik, M. The role of RhoA in tissue polarity and Frizzled signaling. Nature 387, 292–295 (1997)

    Article  ADS  CAS  Google Scholar 

  24. Luo, L., Liao, Y. J., Jan, L. Y. & Jan, Y. N. Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. Genes Dev. 8, 1787–1802 (1994)

    Article  CAS  Google Scholar 

  25. Eaton, S., Auvinen, P., Luo, L., Jan, Y. N. & Simons, K. CDC42 and Rac1 control different actin-dependent processes in the Drosophila wing epithelium. J. Cell Biol. 131, 151–164 (1995)

    Article  CAS  Google Scholar 

  26. Sullivan, W., Ashburner, M. & Hawley, R. S. Drosophila Protocols (Cold Spring Harbor Laboratory Press, New York, 2000)

    Google Scholar 

  27. Patel, N. H., Snow, P. M. & Goodman, C. S. Characterization and cloning of fasciclin III: a glycoprotein expressed on a subset of neurons and axon pathways in Drosophila. Cell 48, 975–988 (1987)

    Article  CAS  Google Scholar 

  28. Frydman, H. M. & Spradling, A. C. The receptor-like tyrosine phosphatase Lar is required for epithelial planar polarity and for axis determination within Drosophila ovarian follicles. Development 128, 3209–3220 (2001)

    CAS  PubMed  Google Scholar 

  29. Jiang, J., Kosman, D., Ip, Y. T. & Levine, M. The dorsal morphogen gradient regulates the mesoderm determinant twist in early Drosophila embryos. Genes Dev. 5, 1881–1891 (1991)

    Article  CAS  Google Scholar 

  30. Rogers, S. L., Rogers, G. C., Sharp, D. J. & Vale, R. D. Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle. J. Cell Biol. 158, 873–884 (2002)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the Developmental Studies Hybridoma Bank at the University of Iowa, the Bloomington Stock Center, and the Drosophila Genetic Resource Center at the Kyoto Institute of Technology. We thank J. Lengyel for byn–Gal4 and S. Hayashi for UAS-gfp–moesin transgenic strains. This work was supported by grants-in-aid from the Japanese Ministry of Education, Culture, Sports and Science. Author Contributions Experimental work was performed by S.H., R.M., K.T., M.K., S.S., T.S., P.S. and T.A. Data analysis was by S.H., R.M., K.T. and K.M., and project planning was coordinated by S.N., R.M. and K.M.

Author information

Authors and Affiliations

  1. Department of Biological Science and Technology,

    Shunya Hozumi, Reo Maeda, Kiichiro Taniguchi, Maiko Kanai, Syuichi Shirakabe, Takeshi Sasamura & Kenji Matsuno

  2. Genome and Drug Research Center, Tokyo University of Science, 2641 Yamazaki, 278-8510, Chiba, Noda, Japan

    Kenji Matsuno

  3. Institute of Signalling, Developmental Biology & Cancer, UMR6543-CNRS, University of Nice Sophia-Antipolis, Parc Valrose, 06108, Nice, France, Cedex 2

    Pauline Spéder & Stéphane Noselli

  4. Cancer, UMR6543-CNRS, University of Nice Sophia-Antipolis, Parc Valrose, 06108

    Pauline Spéder & Stéphane Noselli

  5. Department of Biological Science, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji, 192-0397, Tokyo, Japan

    Toshiro Aigaki

  6. Department of Physics, Biology, and Informatics, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8512, Yamaguchi, Japan

    Ryutaro Murakami

Authors
  1. Shunya Hozumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reo Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kiichiro Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maiko Kanai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Syuichi Shirakabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takeshi Sasamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pauline Spéder
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stéphane Noselli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Toshiro Aigaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ryutaro Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kenji Matsuno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenji Matsuno.

Ethics declarations

Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Tables

This file contains Supplementary Tables 1 and 2. Supplementary Table 1 summarizes the results of this paper as the percentage of individual animals with handedness defects in each mutant or expression line. Supplementary Table 2 shows the phenocritical periods for inducing the LR defect by Myo31DF knockdown and by GFP–Moe misexpression. (PDF 136 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hozumi, S., Maeda, R., Taniguchi, K. et al. An unconventional myosin in Drosophila reverses the default handedness in visceral organs. Nature 440, 798–802 (2006). https://doi.org/10.1038/nature04625

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature04625

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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