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

Kai Yao, Suo Qiu, Lin Tian, William D. Snider, John G. Flannery, David V. Schaffer, Bo Chen

Research output: Contribution to journalArticle

38 Scopus citations

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 languageEnglish (US)
Pages (from-to)165-178
Number of pages14
JournalCell Reports
Volume17
Issue number1
DOIs
StatePublished - Sep 27 2016

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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)

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