Kim, KevinHung, Ruei-JiunPerrimon, Norbert2021-10-042017-01-09Kim, Kevin, Ruei-Jiun Hung, Norbert Perrimon. "miR-263a Regulates ENaC to Maintain Osmotic and Intestinal Stem Cell Homeostasis in Drosophila." Developmental Cell 40, no. 1 (2017): 23-36. DOI: 10.1016/j.devcel.2016.11.0231534-58071878-1551https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37369657Proper regulation of osmotic balance and response to tissue damage is crucial in maintaining intestinal stem cell (ISC) homeostasis. We found that Drosophila miR-263a downregulates the expression of epithelial sodium channel (ENaC) subunits in enterocytes (ECs) to maintain osmotic and ISC homeostasis. In the absence of miR-263a, the intraluminal surface of the intestine displays dehydration-like phenotypes, Na+ levels are increased in ECs, stress pathways are activated in ECs and ISCs overproliferate. Furthermore, miR-263a mutants have increased bacterial load and expression of antimicrobial peptides. Strikingly, these phenotypes are reminiscent of the pathophysiology of cystic fibrosis (CF) in which loss-of-function mutations in the chloride channel CF transmembrane conductance regulator can elevate the activity of ENaC, suggesting that Drosophila could be used as a model for CF. Finally, we provide evidence that overexpression of miR-183, the human ortholog of miR-263a, can also directly target the expressions of all three subunits of human ENaC.en-USJournal Article2021-10-0410.1016/j.devcel.2016.11.023