Abstract
BackgroundTwo key questions in understanding the genetic control of behaviors are: what genes are involved and how these genes interact. To answer these questions at a systems level, we conducted high-content profiling of Drosophila larval locomotor behaviors for over 100 genotypes.ResultsWe studied 69 genes whose C. elegans orthologs were neuronal signalling genes with significant locomotor phenotypes, and conducted RNAi with ubiquitous, pan-neuronal, or motor-neuronal Gal4 drivers. Inactivation of 42 genes, including the nicotinic acetylcholine receptors nAChRα1 and nAChRα3, in the neurons caused significant movement defects. Bioinformatic analysis suggested 81 interactions among these genes based on phenotypic pattern similarities. Comparing the worm and fly data sets, we found that these genes were highly conserved in having neuronal expressions and locomotor phenotypes. However, the genetic interactions were not conserved for ubiquitous profiles, and may be mildly conserved for the neuronal profiles. Unexpectedly, our data also revealed a possible motor-neuronal control of body size, because inactivation of Rdl and Gαo in the motor neurons reduced the larval body size. Overall, these data established a framework for further exploring the genetic control of Drosophila larval locomotion.ConclusionsHigh content, quantitative phenotyping of larval locomotor behaviours provides a framework for system-level understanding of the gene networks underlying such behaviours.
Highlights
Two key questions in understanding the genetic control of behaviors are: what genes are involved and how these genes interact
As we focused on Drosophila genes whose C. elegans orthologs are locomotor genes, this data set revealed that while many genes are conserved in their involvement in locomotor behaviors and neuronal expression, the genetic interactions were conserved to a much lesser degree
Among the parameter values that we found to be significantly different than wild-type values, most of them were 0.5–2 standard deviations (SDs) away from wild-type values (Fig. 1c). 91% of these 58 genes identified with larval locomotor defects in this study have not been previously associated with any locomotor defects
Summary
Two key questions in understanding the genetic control of behaviors are: what genes are involved and how these genes interact. To answer these questions at a systems level, we conducted high-content profiling of Drosophila larval locomotor behaviors for over 100 genotypes. One method to reveal genetic interactions is epistasis analysis [10], which compares double and single mutant phenotypes to identify enhancing and suppressing effects. In Drosophila, this method requires genetic crosses to generate double mutants, and is not practical for large-scale mapping of many genes. In such cases, high-content profiling becomes an effective method in mapping genetic interactions. High-content profiling was successfully applied to discover gene interaction networks regulating
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