Pleiotropic Effects of Drosophila neuralized on Complex Behaviors and Brain Structure

Abstract

Understanding how genotypic variation influences variation in brain structures and behavioral phenotypes represents a central challenge in behavioral genetics. In Drosophila melanogaster, the neuralized (neur) gene plays a key role in development of the nervous system. Different P-element insertional mutations of neur allow the development of viable and fertile adults with profoundly altered behavioral phenotypes that depend on the exact location of the inserted P element. The neur mutants exhibit reduced responsiveness to noxious olfactory and mechanosensory stimulation and increased aggression when limited food is presented after a period of food deprivation. These behavioral phenotypes are correlated with distinct structural changes in integrative centers in the brain, the mushroom bodies, and the ellipsoid body of the central complex. Transcriptional profiling of neur mutants revealed considerable overlap among ensembles of coregulated genes in the different mutants, but also distinct allele-specific differences. The diverse phenotypic effects arising from nearby P-element insertions in neur provide a new appreciation of the concept of allelic effects on phenotype, in which the wild type and null mutant are at the extreme ends of a continuum of pleiotropic allelic effects.

Neurogenetic networks for startle-induced locomotion in Drosophila melanogaster

“…Only three of these genes (Beadex, Sema-5c, and neur) had previously been documented to affect locomotion (19)(20)(21). Many of these candidate genes affect nervous system development and function, as well as other aspects of development, the cell cycle, and oogenesis and spermatogenesis, consistent with previous observations that genes affecting startle-induced locomotion are highly pleiotropic (5,11,12).…”

“…Previous studies also suggested that a high fraction of the genome is associated with startle-induced locomotion (5). Only three of the candidate genes affecting startle-induced locomotion had been previously linked to effects on locomotor behavior (19)(20)(21). Although many of the candidate genes affect nervous system development and function, others are in known genes that have not been found to affect locomotion, or indeed any behavior, in computationally predicted genes or in regions of the genome with no nearby annotated gene.…”

Complex genetic architecture of Drosophila aggressive behavior

“…These problems can be circumvented by assessing epistatic and pleiotropic effects of single mutations in a common homozygous background. In Drosophila melanogaster, diallel crosses among all mutant alleles affecting the same trait have revealed extensive epistasis (7)(8)(9)(10), whereas studies assessing the same mutations for multiple quantitative traits, including genome-wide variation in gene expression, have shown that pleiotropy is pervasive (10)(11)(12)(13). However, pleiotropic effects of epistatic interactions have not been well-explored.…”

“…However, pleiotropic effects of epistatic interactions have not been well-explored. Here, we assess the contribution of epistasis and pleiotropy to the genetic architecture of aggression in Drosophila in a diallel cross among P-element mutations associated with hyperaggressive behavior (13)(14)(15).…”

“…Increased aggression is associated with mutations in androgen and estrogen signaling in vertebrates (30) and sex determination in Drosophila (31,32). Genes involved in brain development or synaptogenesis have been associated with aggression in mice (33) and Drosophila (13,15,20), whereas in humans, quantitative differences in size or structure of the amygdala and prefrontal cortex have been associated with aggression (34). Studies in Drosophila reveal the complex genetic architecture of aggressive behavior, with a large mutational target size, pleiotropic mutational effects, and evidence of epistatic interactions (13-16, 23, 35, 36).…”