miRNA function during zebrafish retina regeneration

Abstract

Zebrafish spontaneously regenerate their retinas after a variety of retinal insults. Key to regeneration are resident support cells called Müller glia (MG), which respond to injury by reverting to a stem cell-like state and generating progenitor cells that can proliferate, migrate and differentiate into any of the lost retinal cell types. Although studies have identified and characterized a number of genes and signaling pathways that control distinct steps of the regeneration process, very little is known about how expression of these genes is regulated. Small non-coding RNAs called microRNAs (miRNAs) regulate regeneration of various tissues in lower vertebrates. However, the functions and overall requirement of miRNAs for zebrafish retina regeneration are poorly understood. Using in vivo loss-of-function studies, we demonstrate that miRNAs are required for normal initiation and progression of retina regeneration. Small RNA high throughput sequencing revealed that miRNAs expression is dynamic during regeneration, but returned to its basal expression levels once regeneration was completed. We characterize the functions of two miRNAs that were downregulated during regeneration, miR-203 and miR-216, and discover that they regulate progenitor cell proliferation and MG dedifferentiation, respectively, during adult zebrafish retina regeneration.