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Millington, Jason William

University of British Columbia

Sexual size dimorphism (SSD) is common throughout the animal kingdom. In the fruit fly, Drosophila melanogaster, females are ~30% larger than males. Over the past two decades, studies in Drosophila have expanded our knowledge of the genetic and dietary requirements for growth. However, it remains incompletely understood how males and females differ in the regulation of growth. The insulin/insulin-like growth factor signaling pathway (IIS) was found to be a key regulator of nutrient-dependent growth and body size. The appropriate coupling of growth with dietary nutrients is known as body size plasticity. Recent studies have implicated both dietary nutrients and IIS in establishing SSD, but the mechanism remains poorly understood. To better understand how males and females differ in growth, I used Drosophila to perform a series of studies examining the contribution of nutrients and IIS on growth in both sexes. In Chapter 2, I found that IIS activity is required for increased female body size. Further, genetically augmenting IIS in males is sufficient for increased body size. In Chapter 3, I build upon this characterization and identify that in a high protein dietary context, females increase IIS activity and body size more than males. This results in increased female body size plasticity. Specifically, when dietary protein is abundant, females produce high levels of the insulinotropic factor Stunted which promotes increased IIS and larger body size. This mechanism was dependent on the sex determination gene transformer. These findings elucidate a molecular mechanism underlying the sex difference in body size plasticity. In Chapter 4, I present evidence that in a low-sugar dietary context both sexes increase growth via distinct mechanisms to achieve the same phenotype. Specifically, males increase IIS activity whereas females increase target of rapamycin (TOR) signaling to reach a larger body size. Together, my thesis provides novel mechanistic insight into how males and females differ in their phenotypic response to genetic manipulation and dietary manipulation. This work provides the basis for future studies to identify conserved sex differences in the regulation of nutrient-responsive pathways, and ultimately will inform our knowledge of the sex-biased risk of human metabolic disease.

Text

2021-08-11

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/79263

Cell and Developmental Biology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/