Ten-a Affects the Fusion of Central Complex Primordia in Drosophila

Quantitative genetics has primarily focused on describing genetic effects on trait means and largely ignored the effect of alternative alleles on trait variability, potentially missing an important axis of genetic variation contributing to phenotypic differences among individuals. To study the genetic effects on individual-to-individual phenotypic variability (or intragenotypic variability), we used Drosophila inbred lines and measured the spontaneous locomotor behavior of flies walking individually in Y-shaped mazes, focusing on variability in locomotor handedness, an assay optimized to measure variability. We discovered that some lines had consistently high levels of intragenotypic variability among individuals, whereas lines with low variability behaved as although they tossed a coin at each left/right turn decision. We demonstrate that the degree of variability is itself heritable. Using a genome-wide association study (GWAS) for the degree of intragenotypic variability as the phenotype across lines, we identified several genes expressed in the brain that affect variability in handedness without affecting the mean. One of these genes, Ten-a, implicates a neuropil in the central complex of the fly brain as influencing the magnitude of behavioral variability, a brain region involved in sensory integration and locomotor coordination. We validated these results using genetic deficiencies, null alleles, and inducible RNAi transgenes. Our study reveals the constellation of phenotypes that can arise from a single genotype and shows that different genetic backgrounds differ dramatically in their propensity for phenotypic variabililty. Because traditional mean-focused GWASs ignore the contribution of variability to overall phenotypic variation, current methods may miss important links between genotype and phenotype.variability | variance QTL | DGRP | ten-a | personality

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“…This stage coincides with a spike in Ten-a expression (Fig. 3C) and the formation of the central complex (28,29).…”

Section: Resultsmentioning

confidence: 57%

Behavioral idiosyncrasy reveals genetic control of phenotypic variability

Ayroles

Buchanan²,

O’Leary

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

171

207

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“…A critical question is how the Teneurins regulate such diverse processes as neuronal wiring, synapse organization, morphogenesis, and patterning. In Drosophila , only two Teneurins exist, but regulate all of these events (Baumgartner et al, 1994 ; Levine et al, 1994 ; Kinel-Tahan et al, 2007 ; Zheng et al, 2011 ; Hong et al, 2012 ; Mosca et al, 2012 ; Cheng et al, 2013 ; Mosca and Luo, 2014 ). The Teneurins likely recognize other cells based on Teneurin expression and differentiate between simultaneously occurring homo- and heterophilic pairs.…”

Section: How Do Teneurins Regulate Synaptic Organization?mentioning

confidence: 99%

On the Teneurin track: a new synaptic organization molecule emerges

Mosca

2015

Front. Cell. Neurosci.

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To achieve proper synaptic development and function, coordinated signals must pass between the pre- and postsynaptic membranes. Such transsynaptic signals can be comprised of receptors and secreted ligands, membrane associated receptors, and also pairs of synaptic cell adhesion molecules. A critical open question bridging neuroscience, developmental biology, and cell biology involves identifying those signals and elucidating how they function. Recent work in Drosophila and vertebrate systems has implicated a family of proteins, the Teneurins, as a new transsynaptic signal in both the peripheral and central nervous systems. The Teneurins have established roles in neuronal wiring, but studies now show their involvement in regulating synaptic connections between neurons and bridging the synaptic membrane and the cytoskeleton. This review will examine the Teneurins as synaptic cell adhesion molecules, explore how they regulate synaptic organization, and consider how some consequences of human Teneurin mutations may have synaptopathic origins.

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“…Of these, No-bridge , central-complex-deranged , and central-body-defect ( cbd KS96 ) showed a significant increase in individual variation in turning as compared to heterozygous controls (Fig 3a). cbd KS96 is an missense mutant of Ten-a 18 , a transmembrane protein involved in axon targeting and synapse formation 19,20 , and causes severe and widespread defects in the fan-shaped body (FB), ellipsoid body (EB), and noduli (No), leading to high individual-to-individual variation in the gross morphology of the CC 10 . Thus, variability in the structure and function of central complex circuits may give rise to variability in turn bias.…”

mentioning

confidence: 99%

Neuronal control of locomotor handedness in Drosophila

Buchanan¹,

Kain²,

Bivort

2014

Preprint

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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.

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Ten-a Affects the Fusion of Central Complex Primordia in Drosophila

Cited by 7 publications

References 39 publications

Behavioral idiosyncrasy reveals genetic control of phenotypic variability

Behavioral idiosyncrasy reveals genetic control of phenotypic variability

On the Teneurin track: a new synaptic organization molecule emerges

Neuronal control of locomotor handedness in Drosophila

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