Journal: Cell reports
Article Title: Wnt Regulates Proliferation and Neurogenic Potential of MŸller Glial Cells via a Lin28/let-7 miRNA-Dependent Pathway in Adult Mammalian Retinas.
PMID/MRN: 27681429
Publication Date: 2016-Sep-27
Abstract:
In cold-blooded vertebrates such as zebrafish, MŸller glial cells (MGs) readily proliferate to replenish lost retinal neurons. In mammals, however, MGs lack regenerative capability as they do not spontaneously re-enter the cell cycle unless the retina is injured. Here, we show that gene transfer of ?-catenin in adult mouse retinas activates Wnt signaling and MG proliferation without retinal injury. Upstream of Wnt, deletion of GSK3? stabilizes ?-catenin and activates MG proliferation. Downstream of Wnt, ?-catenin binds to the Lin28 promoter and activates transcription. Deletion of Lin28 abolishes ?-catenin-mediated effects on MG proliferation, and Lin28 gene transfer stimulates MG proliferation. We further demonstrate that let-7 miRNAs are critically involved in Wnt/Lin28-regulated MG proliferation. Intriguingly, a subset ofÊcell-cycle-reactivated MGs express markers for amacrine cells. Together, these results reveal a key role of Wnt-Lin28-let7 miRNA signaling in regulating proliferation and neurogenic potential of MGs in the adult mammalian retina.
Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.