PUBLICATION
The miR-216a-Dot1l Regulatory Axis Is Necessary and Sufficient for Müller Glia Reprogramming during Retina Regeneration
- Authors
- Kara, N., Kent, M.R., Didiano, D., Rajaram, K., Zhao, A., Summerbell, E.R., Patton, J.G.
- ID
- ZDB-PUB-190822-14
- Date
- 2019
- Source
- Cell Reports 28: 2037-2047.e4 (Journal)
- Registered Authors
- Patton, James G.
- Keywords
- Dot1l, Müller glia, Wnt, miRNA, regeneration, reprogramming, retina, zebrafish
- MeSH Terms
-
- Animals
- Base Sequence
- Cell Dedifferentiation
- Cell Proliferation
- Cellular Reprogramming*
- Ependymoglial Cells/cytology
- Ependymoglial Cells/metabolism*
- Light
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- Nerve Regeneration/physiology*
- Photoreceptor Cells, Vertebrate/metabolism
- Retina/physiology*
- Wnt Signaling Pathway
- Zebrafish/genetics*
- Zebrafish/physiology*
- Zebrafish Proteins/metabolism*
- PubMed
- 31433981 Full text @ Cell Rep.
Citation
Kara, N., Kent, M.R., Didiano, D., Rajaram, K., Zhao, A., Summerbell, E.R., Patton, J.G. (2019) The miR-216a-Dot1l Regulatory Axis Is Necessary and Sufficient for Müller Glia Reprogramming during Retina Regeneration. Cell Reports. 28:2037-2047.e4.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping