| First Author | Yao K | Year | 2016 |
| Journal | Cell Rep | Volume | 17 |
| Issue | 1 | Pages | 165-178 |
| PubMed ID | 27681429 | Mgi Jnum | J:240573 |
| Mgi Id | MGI:5887177 | Doi | 10.1016/j.celrep.2016.08.078 |
| Citation | Yao K, et al. (2016) Wnt Regulates Proliferation and Neurogenic Potential of Muller Glial Cells via a Lin28/let-7 miRNA-Dependent Pathway in Adult Mammalian Retinas. Cell Rep 17(1):165-78 |
| abstractText | In cold-blooded vertebrates such as zebrafish, Muller 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 beta-catenin in adult mouse retinas activates Wnt signaling and MG proliferation without retinal injury. Upstream of Wnt, deletion of GSK3beta stabilizes beta-catenin and activates MG proliferation. Downstream of Wnt, beta-catenin binds to the Lin28 promoter and activates transcription. Deletion of Lin28 abolishes beta-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 of cell-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. |
