Epithelial tissues are continuously being challenged by diverse types of external stresses, therefore, they have evolved protective mechanisms that allow them to regenerate. Yet, our knowledge of the signalling pathways regulating the maintenance of epithelial homeostasis is still limited. The adult Drosophila melanogaster intestinal epithelium is constantly being replaced by new cells deriving from intestinal stem cells (ISCs). This response is enhanced when the tissue gets damaged; however, which signals are activated after damage and how they promote ISC proliferation is poorly understood. Due to its striking similarities to the mammalian epithelium, the adult fly intestine serves as an excellent model system to identify conserved regenerative processes. The main objective of this project is to identify proteins that respond to bacterial- and detergent-induced damage and determine how they promote ISC proliferation. We found an important function for Src to induce ISC proliferation through two different signalling pathways. Furthermore, the intestinal trachea is a network of air tubules responsible for providing oxygen to the intestinal epithelium, similar to our vasculature. It has been reported that bacterial damage to the midgut triggers cellular remodelling of the trachea. Here, we have established two new pathways of communication between the intestinal epithelium and the trachea in response to bacterial damage, but further investigation is warranted to enhance our understanding of this interplay. Overall, this work will give us a better understanding of our own intestinal epithelium, potentially allowing us to develop therapies for inflammatory diseases and even cancer through tissue regeneration.
Identifying damage-induced signalling that promote adult Drosophila midgut regeneration
Legido, M. (Author). 19 Mar 2024
Student thesis: Master's Thesis › Master of Science by Research (MScR)