Nature Communications 2023 February 24. doi: 10.1038/s41467-023-36644-4

Asymmetric activity of NetrinB controls laterality of the Drosophila brain

François Lapraz1, Céline Boutres1, Cloé Fixary-Schuster1, Bruna R. De Queiroz1, Pierre-Yves Plaçais2, Delphine Cerezo1, Florence Besse1, Thomas Préat2, Stéphane Noselli1

1Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose; 06108, Nice, France.
2Plasticité du Cerveau, UMR 8249, CNRS, ESPCI Paris, PSL Research University, Paris, France.



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.

Figure legend: Montage of images of H neurons in normal individuals (left panel), where right (R) and left (L) neurons can be seen projecting their axons into the right asymmetrical body (CAD). In mutants for the NetrinB pathway (NetB, unc-5, fra), these neurons lose their asymmetry and project their axons to both the right and left of the brain (right panel). Symmetric individuals lose long-term memory.

DOI: 10.1038/s41467-023-36644-4