The effects of IIS/TOR signaling on gene expression in Drosophila males and females: IIS/TOR impacts sex-differential gene expression

The insulin signaling pathway is known to interact directly and indirectly with the sex determination regulatory hierarchy, playing a role in directing sexually dimorphic traits. To understand the degree to which the insulin signaling pathway contributes to sexually dimorphic gene expression in adult animals, we examined the effect of perturbation of the pathway on gene expression in male and female Drosophila. Our data reveal a large effect of insulin signaling on expression in adult males and females, with greater than 50% of genes examined changing expression. Males and females have a shared gene expression response to knock-down of InR function, with significant enrichment for pathways involved in metabolism. However, perturbation of insulin signaling has a greater impact on gene expression in males, with more genes changing expression and with a larger magnitude of changes overall. Primarily as a consequence of the response in males, we find that reduced insulin signaling results in a striking increase in sex-differential expression. This includes sex-differences in expression of immune, defense and stress response genes, as well as genes in the insulin signaling pathway itself. Our results demonstrate that perturbation of insulin signaling results in thousands of genes displaying sex differences in expression that are not differentially expressed in control conditions. Thus, insulin signaling may play a role in variability of sex-differential expression observed in studies of adult somatic tissues.