Wnt Regulates Proliferation and Neurogenic Potential of Muller Glial Cells via a Lin28/let-7 miRNA-Dependent Pathway in Adult Mammalian Retinas.

ABSTRACT: In cold-blooded vertebrates such as zebrafish, Müller 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 β-catenin in adult mouse retinas activates Wnt signaling and MG proliferation without retinal injury. Upstream of Wnt, deletion of GSK3β stabilizes β-catenin and activates MG proliferation. Downstream of Wnt, β-catenin binds to the Lin28 promoter and activates transcription. Deletion of Lin28 abolishes β-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 prol

SUBMITTER: Yao K 

PROVIDER: S-EPMC5076887 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature