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.

Type ID unconventional myosin controls left–right asymmetry in Drosophila

Nature volume 440, pages 803–807 (2006)Cite this article

Abstract

Breaking left–right symmetry in Bilateria embryos is a major event in body plan organization that leads to polarized adult morphology, directional organ looping, and heart and brain function1,2,3,4. However, the molecular nature of the determinant(s) responsible for the invariant orientation of the left–right axis (situs choice) remains largely unknown. Mutations producing a complete reversal of left–right asymmetry (situs inversus) are instrumental for identifying mechanisms controlling handedness, yet only one such mutation has been found in mice (inversin)5 and snails6,7. Here we identify the conserved type ID unconventional myosin 31DF gene (Myo31DF) as a unique situs inversus locus in Drosophila. Myo31DF mutations reverse the dextral looping of genitalia, a prominent left–right marker in adult flies. Genetic mosaic analysis pinpoints the A8 segment of the genital disc as a left–right organizer and reveals an anterior–posterior compartmentalization of Myo31DF function that directs dextral development and represses a sinistral default state. As expected of a determinant, Myo31DF has a trigger-like function and is expressed symmetrically in the organizer, and its symmetrical overexpression does not impair left–right asymmetry. Thus Myo31DF is a dextral gene with actin-based motor activity controlling situs choice. Like mouse inversin8, Myo31DF interacts and colocalizes with β-catenin, suggesting that situs inversus genes can direct left–right development through the adherens junction.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

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

Figure 1: Myosin31DF controls directional organ looping in Drosophila.
Figure 2: Spatial expression of Myo31DF in the A8 segment of the genital disc and its interaction with Armadillo.
Figure 3: Spatial and temporal organization of Myo31DF function in the left–right organizer.

References

  1. Bisgrove, B. W., Morelli, S. H. & Yost, H. J. Genetics of human laterality disorders: insights from vertebrate model systems. Annu. Rev. Genomics Hum. Genet. 4, 1–32 (2003)

    Article  CAS  Google Scholar 

  2. Levin, M. Left–right asymmetry in embryonic development: a comprehensive review. Mech. Dev. 122, 3–25 (2005)

    Article  CAS  Google Scholar 

  3. Hamada, H., Meno, C., Watanabe, D. & Saijoh, Y. Establishment of vertebrate left–right asymmetry. Nature Rev. Genet. 3, 103–113 (2002)

    Article  CAS  Google Scholar 

  4. Raya, A. & Belmonte, J. C. Sequential transfer of left–right information during vertebrate embryo development. Curr. Opin. Genet. Dev. 14, 575–581 (2004)

    Article  CAS  Google Scholar 

  5. Morgan, D. et al. Inversin, a novel gene in the vertebrate left–right axis pathway, is partially deleted in the inv mouse. Nature Genet. 20, 149–156 (1998)

    Article  CAS  Google Scholar 

  6. Ueshima, R. & Asami, T. Evolution: single-gene speciation by left–right reversal. Nature 425, 679 (2003)

    Article  ADS  CAS  Google Scholar 

  7. Freeman, G. & Lundelius, J. The developmental genetics of dextrality and sinistrality in the gastropod Lymnaea peregra. Wilhelm Roux's Archives 191, 69–83 (1982)

    Article  Google Scholar 

  8. Nurnberger, J., Bacallao, R. L. & Phillips, C. L. Inversin forms a complex with catenins and N-cadherin in polarized epithelial cells. Mol. Biol. Cell 13, 3096–3106 (2002)

    Article  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. Gleichauf, R. Anatomie und variabilität des geschlechtsapparates von Drosophila melanogaster (Meigen). Z. Wiss. Zool. 148, 1–66 (1936)

    Google Scholar 

  11. 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 

  12. Morgan, D. et al. The left–right determinant inversin has highly conserved ankyrin repeat and IQ domains and interacts with calmodulin. Hum. Genet. 110, 377–384 (2002)

    Article  CAS  Google Scholar 

  13. Eley, L. et al. A perspective on inversin. Cell Biol. Int. 28, 119–124 (2004)

    Article  CAS  Google Scholar 

  14. Bahler, M. & Rhoads, A. Calmodulin signaling via the IQ motif. FEBS Lett. 513, 107–113 (2002)

    Article  CAS  Google Scholar 

  15. Casares, F., Sanchez, L., Guerrero, I. & Sanchez-Herrero, E. The genital disc of Drosophila melanogaster. 1. Segmental and compartmental organization. Dev. Genes Evol. 207, 216–228 (1997)

    Article  CAS  Google Scholar 

  16. Chen, E. H. & Baker, B. S. Compartmental organization of the Drosophila genital imaginal discs. Development 124, 205–218 (1997)

    CAS  PubMed  Google Scholar 

  17. Freeland, D. E. & Kuhn, D. T. Expression patterns of developmental genes reveal segment and parasegment organization of D. melanogaster genital discs. Mech. Dev. 56, 61–72 (1996)

    Article  CAS  Google Scholar 

  18. Sanchez, L., Casares, F., Gorfinkiel, N. & Guerrero, I. The genital disc of Drosophila melanogaster. 2. Role of the genes hedgehog, decapentaplegic and wingless. Dev. Genes Evol. 207, 229–241 (1997)

    Article  CAS  Google Scholar 

  19. Watanabe, D. et al. The left–right determinant inversin is a component of node monocilia and other 9 + 0 cilia. Development 130, 1725–1734 (2003)

    Article  CAS  Google Scholar 

  20. Bobinnec, Y., Marcaillou, C. & Debec, A. Microtubule polyglutamylation in Drosophila melanogaster brain and testis. Eur. J. Cell Biol. 78, 671–674 (1999)

    Article  CAS  Google Scholar 

  21. Dubruille, R. et al. Drosophila regulatory factor X is necessary for ciliated sensory neuron differentiation. Development 129, 5487–5498 (2002)

    Article  CAS  Google Scholar 

  22. Bonnafe, E. et al. The transcription factor RFX3 directs nodal cilium development and left–right asymmetry specification. Mol. Cell. Biol. 24, 4417–4427 (2004)

    Article  CAS  Google Scholar 

  23. Macias, A. et al. PVF1/PVR signaling and apoptosis promotes the rotation and dorsal closure of the Drosophila male terminalia. Int. J. Dev. Biol. 48, 1087–1094 (2004)

    Article  CAS  Google Scholar 

  24. 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 

  25. Garcia-Castro, M. I., Vielmetter, E. & Bronner-Fraser, M. N-Cadherin, a cell adhesion molecule involved in establishment of embryonic left–right asymmetry. Science 288, 1047–1051 (2000)

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Bertet, C., Sulak, L. & Lecuit, T. Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429, 667–671 (2004)

    Article  ADS  CAS  Google Scholar 

  28. Strutt, H. & Strutt, D. EGF signaling and ommatidial rotation in the Drosophila eye. Curr. Biol. 13, 1451–1457 (2003)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the Bloomington Stock Center, B. Durand, B. Edde, A. Laurençon, V. van de Bor, J. P. Vincent and M. L. Cariou for materials and fly lines; E. Sanchez-Herrero for AbdB–Gal4; Y. Bellaiche and M. Morgan for GST–Arm protein; C. Mionnet for help with GST-pulldown assays; and C. Featherstone, P. Follette, E. Sanchez-Herrero, M. Suzanne, L. Wolpert and laboratory members for critically reading the manuscript. This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Ministère de l'éducation et de la Recherche (ACI), the Hungarian National Scientific Research Fund (OTKA), the Association pour la Recherche contre le Cancer (ARC) and the EMBO Young Investigator Programme.

Author information

Author notes

  1. Pauline Spéder and Géza Ádám: *These authors contributed equally to this work

Authors and Affiliations

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

    Pauline Spéder, Géza Ádám & Stéphane Noselli

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

    Pauline Spéder, Géza Ádám & Stéphane Noselli

  3. Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, PO Box 521, H-6701, Szeged, Hungary

    Géza Ádám

Authors
  1. Pauline Spéder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Géza Ádám
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stéphane Noselli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stéphane Noselli.

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 Data

This file contains figure legends for Supplementary Figures 1–6 as well as Supplementary Methods (DOC 25 kb)

Supplementary Table 1

Direction of genitalia rotation in several Drosophila species. (DOC 28 kb)

Supplementary Figure 1

Myo31DF is a conserved type ID unconventional myosin that colocalizes with F-actin. (PDF 2562 kb)

Supplementary Figure 2

Characterization of anti-Myo31DF antibodies. (PDF 215 kb)

Supplementary Figure 3

Developmental expression pattern of Myo31DF in the genital disc. (PDF 381 kb)

Supplementary Figure 4

Expression pattern of Ptc-GAL4 in the A8 segment. (PDF 410 kb)

Supplementary Figure 5

Schematic representation of the non-rotated phenotype. (PDF 105 kb)

Supplementary Figure 6

Interaction between Myo31DF and Armadillo. (PDF 156 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Spéder, P., Ádám, G. & Noselli, S. Type ID unconventional myosin controls left–right asymmetry in Drosophila. Nature 440, 803–807 (2006). https://doi.org/10.1038/nature04623

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature04623

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