Neuronal control of locomotor handedness in Drosophila

Abstract

Handedness in humans – better performance using either the left or right hand – is personally familiar, moderately heritable1, and regulated by many genes2, including those involved in general body symmetry3. But behavioral handedness, i.e. lateralization, is a multifaceted phenomenon. For example, people display clockwise or counter-clockwise biases in their walking behavior that is uncorrelated to their hand dominance4,5, and lateralized behavioral biases have been shown in species as disparate as mice (paw usage6), octopi (eye usage7), and tortoises (side rolled on during righting8). However, the mechanisms by which asymmetries are instilled in behavior are unknown, and a system for studying behavioral handedness in a genetically tractable model system is needed. Here we show that Drosophila melanogaster flies exhibit striking variability in their left-right choice behavior during locomotion. Very strongly biased "left-handed" and "right-handed" individuals are common in every line assayed. The handedness of an individual persists for its lifetime, but is not passed on to progeny, suggesting that mechanisms other than genetics determine individual handedness. We use the Drosophila transgenic toolkit to map a specific set of neurons within the central complex that regulates the strength of behavioral handedness within a line. These findings give insights into choice behaviors and laterality in a simple model organism, and demonstrate that individuals from isogenic populations reared under experimentally identical conditions nevertheless display idiosyncratic behaviors.

Behavioral idiosyncrasy reveals genetic control of phenotypic variability

“…The effect of RNAi knockdown suggests a quantitative relationship between Ten-a mean expression and variance in turning bias. The bias in handedness of a given fly is a fixed property of that individual (e.g., a young adult with a strong left bias will display this bias throughout its life) (18). The persistence of this bias suggests that handedness may be wired during development.…”

“…In a companion study, Buchanan et al (18) mapped a set of neurons within the central complex (i.e., protocerebral bridge columnar neurons) that regulates the magnitude of left-right turn bias and therefore the magnitude of intragenotypic variability. Together these studies constitute a rare example linking natural genetic variation for a complex behavioral trait, to mutants implicating a brain region, to a specific subcircuit within this region.…”

“…Further details about the assay are provided in ref. 18; the code is available at lab.debivort.org/neuronal-control-of-locomotor-handedness/.…”

“…1A). Specifically, we measured the spontaneous locomotor behavior of flies walking individually in Y-shaped mazes (18), focusing on the variability in locomotor handedness (left-right turning bias). The precision and high-throughput nature of our assays allows a large number of flies to be measured per genotype and permits robust estimates of the sampling error on variance itself.…”

Behavioral individuality reveals genetic control of phenotypic variability

“…These genes are strongly enriched for expression in the central nervous system both in adults and in larvae (adult CNS enrichment in adult FET p < 0.001 and in larvae FET p < 0.01, data from FlyAtlas 25 ) (Supplementary Fig 4). Among these, the synaptic target recognition gene Tenascin accessory (Ten-a, GWAS p < 3 × 10 -6 ) (Fig 3a) caught our attention, Ten-a is a transmembrane signaling protein involved in synapse formation 26,27 , critical to the development of the brain central complex 5 (a brain structure implicated in sensory integration and locomotion [4][5][6]28 ) and is highly conserved from insects to mammals 29 . In order to validate the role of Ten-a in modulating variability in turning bias, we used a null allele (Tena cbd-KS9635 ), a deficiency overlapping Ten-a (Df(1)Ten-a 26 ), and expression knock-down using RNAi (UAS-TRiP.JF03375 30 ).…”