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Millington, J. W.

Publications and source records attributed to Millington, J. W..

2 recordsLinked to original sources

Genetic manipulation of insulin/insulin-like growth factor signaling pathway activity has sex-biased effects on Drosophila body size

In Drosophila, female body size is approximately 30% larger than male body size due to an increased rate of larval growth. While the mechanisms that control this sex difference in body size remain incompletely understood, recent studies suggest that the insulin/insulin-like growth factor signaling pathway (IIS) plays a role in the sex-specific regulation of growth during development. In larvae, IIS activity differs between the sexes, and there is evidence of sex-specific regulation of IIS ligands. Yet, we lack knowledge of how changes to IIS activity impact growth in each sex, as the majority of studies on IIS and body size use single- or mixed-sex groups of larvae and/or adult flies. The goal of our current study was to clarify the requirement for IIS activity in each sex during the larval growth period. To achieve this goal we used established genetic approaches to enhance, or inhibit, IIS activity, and quantified body size in male and female larvae. Overall, genotypes that inhibited IIS activity caused a female-biased decrease in body size, whereas genotypes that augmented IIS activity caused a male-specific increase in body size. This data extends our current understanding of larval growth by showing that most changes to IIS pathway activity have sex-biased effects on body size, and highlights the importance of analyzing data by sex in larval growth studies.

physiology

Female-specific upregulation of insulin pathway activity mediates the sex difference in Drosophila body size plasticity

Nutrient-dependent body size plasticity differs between the sexes in most species, including mammals. Previous work in Drosophila showed that body size plasticity was higher in females, yet the mechanisms underlying the sex difference in body size plasticity remain unclear. Here, we discover that a protein-rich diet augments body size in females and not males because of a female-specific increase in activity of the conserved insulin/insulin-like growth factor signaling pathway (IIS). This increased IIS activity was triggered by a diet-induced increase in stunted, and required Drosophila insulin-like peptide 2, illuminating new sex-specific roles for these genes. Importantly, we show that sex determination gene transformer regulates the diet-induced increase in stunted and IIS activity, and mediates the sex difference in body size plasticity. This identifies one sex-specific mechanism underlying the nutrient-dependent regulation of IIS activity and body size plasticity, providing vital insight into conserved mechanisms that mediate sex differences in phenotypic plasticity.

physiology