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The miR-216a-Dot1l Regulatory Axis Is Necessary and Sufficient for Müller Glia Reprogramming during Retina Regeneration

Authors :
Nergis Kara
Matthew R Kent
James G. Patton
Anna Zhao
Dominic Didiano
Emily R. Summerbell
Kamya Rajaram
Source :
Cell Reports, Vol 28, Iss 8, Pp 2037-2047.e4 (2019), Cell reports
Publication Year :
2019
Publisher :
Elsevier, 2019.

Abstract

SUMMARY Unlike the adult mammalian retina, Müller glia (MG) in the adult zebrafish retina are able to dedifferentiate into a ‘‘stem cell’’-like state and give rise to multipotent progenitor cells upon retinal damage. We show that miR-216a is downregulated in MG after constant intense light lesioning and that miR-216a suppression is necessary and sufficient for MG dedifferentiation and proliferation during retina regeneration. miR-216a targets the H3K79 methyltransferase Dot1l, which is upregulated in proliferating MG after retinal damage. Loss-of-function experiments show that Dot1l is necessary for MG reprogramming and mediates MG proliferation downstream of miR-216a. We further demonstrate that miR-216a and Dot1l regulate MG-mediated retina regeneration through canonical Wnt signaling. This article reports a regulatory mechanism upstream of Wnt signaling during retina regeneration and provides potential targets for enhancing regeneration in the adult mammalian retina.<br />Graphical Abstract<br />In Brief Unlike the adult mammalian retina, Müller glia in the adult zebrafish retina are able to reprogram into a stem cell-like state and give rise to multipotent progenitor cells upon retinal damage. Kara et al. show that miR-216a suppression stimulates Müller glia reprogramming through upregulation of the H3K79 methyltransferase Dot1l and activation of Wnt/β-catenin signaling.

Details

Language :
English
ISSN :
22111247
Volume :
28
Issue :
8
Database :
OpenAIRE
Journal :
Cell Reports
Accession number :
edsair.doi.dedup.....5393d3f5b1e1d8501b0bc30d528ad24c