Type ID unconventional myosin controls left-right asymmetry in Drosophila

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(1-4). 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 inversin(8), Myo31DF interacts and colocalizes with beta-catenin, suggesting that situs inversus genes can direct left - right development through the adherens junction.