Exploring the roles of the sex determinant Doublesex in the adult gut of Drosophila melanogaster

Abstract

Molecular and cellular sexual dimorphisms contribute to the establishment of sex differences in various aspects of physiology. There is an increasing realization that the incidence and/or prognosis of many disorders differs between sexes, with incomplete understanding of the underlying mechanisms. In Drosophila melanogaster, the molecular pathway determining sexual traits is well studied, particularly in the reproductive and nervous systems. Previous work from our lab and others have characterised the expression of the last effector in the sex determination pathway, Doublesex, in somatic tissues such as the intestine. In this thesis I have validated that Dsx has a sex- and cell type-specific expression in the midgut, being only detected in male enterocytes. The fly intestine is an excellent system to study physiology, mostly because of its metabolic roles and adaptability towards internal/external environmental changes; and sexual dimorphism in anatomy, proliferation, immunity and metabolism. I have investigated contributions of the intrinsic sexual fate of enterocytes by exploring the roles of Dsx. To start characterizing its functions, I have downregulated dsx in adult enterocytes and sought to identify downstream targets using transcriptomics. I have begun to describe its effects on the expression of lipid genes, for example on the female enriched CG17192 lipase, and assessed the changes in intestinal lipid droplets and whole-body fat. Finally, I have unravelled a novel function of the oncogene Myc in adult enterocytes in regulating lipid processes. Myc expression is higher in female midguts, and its knock-down in enterocytes impacts lipid metabolism and, extrinsically, stem cell proliferation. My work opens up the possibility that Dsx controls lipid metabolism in a sexually dimorphic manner via the indirect/direct control of Myc, warranting further examination. This thesis reveals a new concept of Dsx and Myc establishing sexual dimorphism of lipids from the enterocytes, potentially affecting proliferation, disease incidence and reproductive success.