# Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity

## TL;DR

This study shows how asymmetry in Drosophila brain circuits develops through interactions of pioneer neurons and structural plasticity.

## Contribution

The study reveals a novel mechanism of circuit asymmetry formation via axonal interactions and dynamic adhesion molecule expression in Drosophila.

## Key findings

- Directional asymmetry in Drosophila brain circuits arises from axonal interactions of bilateral pioneer neurons.
- Fasciclin 2 expression maintains structural plasticity during axonal remodeling for circuit lateralization.
- Reduced circuit asymmetry due to Fasciclin 2 manipulation affects adult brain function.

## Abstract

Structural and functional differences between brain hemispheres are a common feature of animal nervous systems with reduced bilateral asymmetry often linked to impaired cognitive performance. How neuronal left-right asymmetry is initiated and integrated into a bilaterally symmetrical ground pattern is poorly understood. Here, we show that the directional asymmetry of a Drosophila central brain circuit originates from axonal interactions of two types of bilateral pioneer neurons. Subsequent recruitment of neighboring neurons into the asymmetric neuropil primordium results in hemisphere-specific microcircuits. Circuit lateralization requires dynamic expression of the cell adhesion molecule Fasciclin 2 to maintain structural plasticity in axonal remodeling. Reduced circuit asymmetry following cell type–specific Fasciclin 2 manipulation affects adult brain function. These results reveal an unexpected degree of developmental plasticity of late-born Drosophila neurons in the formation of a circuit node via the lateralized recruitment of symmetric circuit components.

Late-born neurons in the developing Drosophila brain induce and integrate left-right asymmetry into bilateral neural circuits.