Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal permeability and survival in Drosophila

Abstract

AbstractExposure to genotoxic stress by environmental agents or treatments, such as radiation therapy, can diminish healthspan and accelerate aging. We have developed aDrosophila melanogastermodel to study the molecular effects of radiation-induced damage and repair. Utilizing a quantitative intestinal permeability assay, we performed an unbiased GWAS screen (using 156 strains from theDrosophilaGenetic Reference Panel) to search for natural genetic variants that regulate radiation-induced gut permeability in adultD. melanogaster. From this screen, we identified an RNA binding protein,Musashi (msi),as one of the possible genes associated with changes in intestinal permeability upon radiation. The overexpression ofmsipromoted intestinal stem cell proliferation, which increased survival after irradiation and rescued radiation-induced intestinal permeability. In summary, we have establishedD. melanogasteras an expedient model system to study the effects of radiation-induced damage to the intestine in adults and have identifiedmsias a potential therapeutic target.