The control of epithelial tissue various stressful conditions, to identify the mechanism of Tis11 function in ISCs, and to establish whether Tis11 activity in ISCs influences age-related changes in homeostasis of the epithelium. Homeostasis requires accurate control of stem cell proliferation in response to a variety of stimuli. A critica aspect of this regulation is the return of stem cells to a quiescent state after a transient burst f regenerative activity. Here, I propose experiments designed to elucidate regulatory mechanisms that control this recovery. I use the Drosophila posterior midgut epithelium as a model to establish the function of the mRNA degradation pathway in stem cell recovery. I have identified the RNA binding protein Tis11 as an inhibitor of stem cell proliferation that is specifically expressed in stem cells. Strikingly, I find that Tis 11 is required for recovery of a quiescent stae in the intestinal epithelium after a mild challenge. I now propose to extend this work to test to te hypothesis that Tis11 is critical for the recovery of quiescent ISCs under times of stressed induced proliferation.
Accurate control of stem cell activity is critical for tissue homeostasis. The applicant will analyze the regulation of stem cell quiescence using the Drosophila midgut epithelium as a genetically accessible model system. Through genetic and biochemical studies, the applicant will test the hypothesis that the RNA binding factor Tis11 plays a central role in the control of quiescence in the intestinal stem cells, and that this regulation is critical to prevent age-related changes in stem cell function.
|McClelland, Lindy; Jasper, Heinrich; Biteau, Benoît (2017) Tis11 mediated mRNA decay promotes the reacquisition of Drosophila intestinal stem cell quiescence. Dev Biol 426:8-16|