1. Institute of Signalling, Developmental Biology & Cancer, UMR6543-CNRS, University of Nice Sophia-Antipolis, Parc Valrose, 06108 Nice Cedex 2, France
2. Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, PO Box 521, Szeged H-6701, Hungary
3. *These authors contributed equally to this work

Correspondence to: Stéphane Noselli¹ Correspondence and requests for materials should be addressed to S.N. (Email: noselli@unice.fr).

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 function^{1, 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 snails^{6, 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 -catenin, suggesting that situs inversus genes can direct left–right development through the adherens junction.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.