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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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.
Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
This file contains figure legends for Supplementary Figures 1–6 as well as Supplementary Methods (DOC 25 kb)
Direction of genitalia rotation in several Drosophila species. (DOC 28 kb)
Myo31DF is a conserved type ID unconventional myosin that colocalizes with F-actin. (PDF 2562 kb)
Characterization of anti-Myo31DF antibodies. (PDF 215 kb)
Developmental expression pattern of Myo31DF in the genital disc. (PDF 381 kb)
Expression pattern of Ptc-GAL4 in the A8 segment. (PDF 410 kb)
Schematic representation of the non-rotated phenotype. (PDF 105 kb)
Interaction between Myo31DF and Armadillo. (PDF 156 kb)
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