Abstract EN:

The establishment of a fixed and invariant Left-Right (LR) asymmetry is crucial for both the structural organization of the body and for organ’s functions, like the heart. Studies led on deuterostomes have proposed elegant models for symmetry breaking, involving Nodal flow or ion flows. However, the molecular nature of the determinant(s) responsible for the LR orientation (situs choice) remains largely unknown, as well as the conservation of early mechanisms during evolution. Our study has identified the conserved type ID unconventional myosin gene (Myo31DF) as a Situs inversus gene in Drosophila. Myo31DF mutations reverse both the dextral looping of genitalia, a prominent LR marker in adult flies, and the positioning of embryonic gut. Genetic mosaic analysis identifies the A8 segment of the genital disc, the precursor of adult genitalia, as a LR organizer, and reveals an anterior–posterior compartmentalization of Myo ID function that directs dextral development (A8p) and represses a sinistral default asymmetry (A8a). As expected of a LR determinant, Myo ID has a trigger-like function, as well as an endogenous symmetric expression, and its symmetric overexpression doesn’t lead to LR defects. We also showed that Myo ID interacts and colocalizes with β-catenin, like the only other molecularly identified Situs inversus gene, the mouse Inversin. It suggests that Situs inversus genes could direct LR development through the adherens junction. We demonstrate here the existence of a LR axis in Drosophila, and identify an actin-dependant molecular motor, Myo ID, as a dextral determinant controlling situs choice, and thus establishment of an invariant asymmetry in a protostome.