Intestinal stem cells (ISCs) in the adult Drosophila midgut are responsible for coordinating intestinal homeostasis and regeneration by dividing to self-renew and give rise to mature cell types in the tissue. Following the discovery that the Drosophila midgut does not degenerate functionally or structurally in the absence of ISC proliferation and tissue turnover, we have investigated different factors that influence the ability of the midgut to maintain basal homeostasis in these conditions. We blocked ISC proliferation by overexpressing cell cycle regulators, Dacapo and Wee1, in the midguts of mated female, virgin female and male Drosophila, as well as female Drosophila fed alternative diets and treated with antibiotics to reduce the microbiome. Homeostatic maintenance in the absence of ISC proliferation is maintained regardless of genetic sex and diet, while reduction in microbiome reduces ISC proliferation in control Drosophila, as well as the ability to maintain tissue size. Moreover, mated female Drosophila experience a failure of intestinal homeostasis as we observe a complete absence of tissue turnover in the control condition and a decline in midgut size. We also observed cells being shed from the epithelium at the same rate in both control midguts and midguts with restricted ISC proliferation, suggesting that cell loss is not reduced as a mechanism of homeostasis. We have also observed instances of increased cell size and decreased cell density at late timepoints in midguts with blocked ISC proliferation. In light of this, we have addressed compensatory cellular hypertrophy as a potential mechanism for homeostasis in the absence of ISC proliferation.
Investigating Factors that Influence Compensatory Mechanisms that Maintain Adult Drosophila Intestinal Homeostasis in the Absence of Intestinal Stem Cell Activity
Duhig, E. R. (Author). 1 Oct 2024
Student thesis: Master's Thesis › Master of Science by Research (MScR)