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 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.
Original language | English (US) |
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Pages (from-to) | 165-178 |
Number of pages | 14 |
Journal | Cell Reports |
Volume | 17 |
Issue number | 1 |
DOIs | |
State | Published - Sep 27 2016 |
Keywords
- cell proliferation
- cell reprogramming
- glial cell reprogramming
- glial-cell-derived neurogenesis
- let-7 miRNA
- lin28 signaling
- retinal regeneration
- Wnt signaling
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)