Musashiexpression in intestinal stem cells attenuates radiation-induced decline in intestinal homeostasis and survival inDrosophila

Exposure to genotoxic stress by environmental agents or treatments, such as radiation therapy, can diminish health span 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 ∼150 strains from the DGRP reference panel) to search for natural genetic variants that regulate radiation-induced gut permeability. From this screen, we identified the RNA binding protein,Musashi (msi).Msioverexpression promoted intestinal stem cell proliferation, which increased survival after irradiation and rescued radiation-induced gut permeability. We identified that a novel role ofMsi inISC proliferation a novel role forMsiin enhancing ISC function following radiation-induced gut damage, which identifiesMsias a potential therapeutic target.