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Date Submitted

Spring 5-4-2012

Research Mentor and Department

Yehuda Ben-Shahar

Restricted/Unrestricted

Dissertation/Thesis

Abstract

In recent years, the field of evolutionary developmental biology has demonstrated that many developmental processes are controlled by conserved genetic programs, even in distantly related species. We hypothesize that conserved genetic programs also control other complex phenotypes, including social behavior. To that end, we seek to identify conserved regulators of social behavior across metazoa. The rare human genetic disorder Williams-Beuren Syndrome (WBS), which is caused by a heterozygous deletion of 26-28 genes on chromosome 7, provides an opportunity to identify such genes. A remarkable phenotype associated with WBS is hypersociability, thereby making all the WBS genes candidates for novel regulators of human social behaviors. Unpublished research from the Ben-Shahar lab already suggests that WBS genes are involved in social decision-making in the honey bee Apis mellifera, as many of the WBS-loci are regulated with the transition from nursing to guarding to foraging. Here, we present evidence that WBS-loci are similarly involved in social decision-making in the fruit fly Drosophila melanogaster. We found that seven of the fourteen WBS homologs in D. melanogaster are regulated in the heads of virgin versus mated females. Virgin females are more receptive to male courtship behavior than are mated females, suggesting that transcriptional regulation of one or several WBS homologs may be responsible for the mated females’ decreased interest in male courtship. Current experiments aim at directly implicating candidate genes in regulating social decision-making. Using a reversed-genetics approach, we seek to knockdown the expression level of each of these seven genes using RNAi transgenes, and to perform behavioral assays of male receptivity in virgin and mated females, in order to show that the expression level of one or several of the seven regulated genes can directly affect females’ decision of whether to mate upon male courtship. In addition, I analyzed publicly available in-situ hybridization data of gene expression in the mouse brain, to identify spatially co-expressed genes in brain regions which may be involved in the WBS hypersocial phenotype. While I found no localized expression pattern shared among WBS genes, many genes showed spatial overlap. The results of my experiments, while not yet conclusive, do suggest that WBS loci are involved in regulation of social decision-making in several species, supporting the hypothesis that conserved genetic programs control social behavior across metazoa.