Integrity of the Barrier Epithelium in Drosophila Gut is Mediated by Factors That Regulate Intestinal Stem Cell Activity
My thesis work on the Drosophila intestinal epithelium (IE) involved characterizing the mitochondrial unfolded protein response (UPRmt), validating proliferation specific regulatory genes, and proposing gut barrier function–specific genes as regulators of commensal bacteria density. The results from this project have shown that intestinal stem cells (ISCs) respond systemically in the presence of autonomously induced, visceral muscle (VM)-localized UPRmt. A phenotypic correlation between autonomous electron transport chain (ETC) dysfunction was observed in the visceral muscle and the systemic UPRmt response of ISCs in the posterior midgut. Exploratively, two genome-wide association studies (GWAS) using the Drosophila genetic reference panel (DGRP) were performed, and genetic candidates with functionally unknown effects on both ISC proliferation and gut flora homeostasis in an aged invertebrate tissue were found. These candidate genesDunce (Dnc), Tfb1 (TF11H Homolog), and Arrowhead (Awh)were validated to be genetic regulators of proliferative homeostasis with age. In addition, I proposed the genes Dystrophin (Dys) and Rolling Pebbles (Rols) to be mediators of microbial density relative to gut barrier integrity. Collectively, the work presented here has contributed to the fundamental understanding of regenerative biology and gerontology by demonstrating phenotypes of functionally novel, stem cell–specific genetic perturbations interpreted as regulatory factors of both ISC maintenance and activity.
Barrier Epithelium, intestinal epithelium, Genetics and Genomics
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