Asymmetric activity of NetrinB controls laterality of the Drosophila brain.

Left-Right (LR) asymmetry of the nervous system is widespread across animals and is thought to be important for cognition and behaviour. But in contrast to visceral organ asymmetry, the genetic basis and function of brain laterality remain only poorly characterized. In this study, we performed RNAi screening to identify genes controlling brain asymmetry in Drosophila. We found that the conserved NetrinB (NetB) pathway is required for a small group of bilateral neurons to project asymmetrically into a pair of neuropils (Asymmetrical Bodies, AB) in the central brain in both sexes. While neurons project unilaterally into the right AB in wild-type flies, netB mutants show a bilateral projection phenotype and hence lose asymmetry. Developmental time course analysis reveals an initially bilateral connectivity, eventually resolving into a right asymmetrical circuit during metamorphosis, with the NetB pathway being required just prior symmetry breaking. We show using unilateral clonal analysis that netB activity is required specifically on the right side for neurons to innervate the right AB. We finally show that loss of NetB pathway activity leads to specific alteration of long-term memory, providing a functional link between asymmetrical circuitry determined by NetB and animal cognitive functions.

Molecular to organismal chirality is induced by the conserved myosin 1D.

The emergence of asymmetry from an initially symmetrical state is a universal transition in nature. Living organisms show asymmetries at the molecular, cellular, tissular, and organismal level. However, whether and how multilevel asymmetries are related remains unclear. In this study, we show that Drosophila myosin 1D (Myo1D) and myosin 1C (Myo1C) are sufficient to generate de novo directional twisting of cells, single organs, or the whole body in opposite directions. Directionality lies in the myosins' motor domain and is swappable between Myo1D and Myo1C. In addition, Myo1D drives gliding of actin filaments in circular, counterclockwise paths in vitro. Altogether, our results reveal the molecular motor Myo1D as a chiral determinant that is sufficient to break symmetry at all biological scales through chiral interaction with the actin cytoskeleton.