Type ID unconventional myosin controls left–right asymmetry in Drosophila (original) (raw)

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.

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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.

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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
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  2. Géza Ádám
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  3. Stéphane Noselli
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Correspondence toStéphane Noselli.

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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

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Editorial Summary

All right now

From flies to humans, the left and right side of the body plan differs. Exactly how symmetry is broken in the early embryo is a mystery. But now two groups working independently report a genetic defect in the fly that may help uncover the mechanism. Both groups studied a mutant with reversed looping of the viscera, and discovered that the mutation lies in an unconventional myosin. Myosin directs right-handed looping and represses the default left-handed fate. This discovery now links actin-based molecular motors and the actin cytoskeleton to left–right patterning in vertebrates.