PUBLICATION
Ascl1a/Dkk/ beta -catenin signaling pathway is necessary and glycogen synthase kinase-3 beta inhibition is sufficient for zebrafish retina regeneration
- Authors
- Ramachandran, R., Zhao, X.F., and Goldman, D.
- ID
- ZDB-PUB-110920-18
- Date
- 2011
- Source
- Proceedings of the National Academy of Sciences of the United States of America 108(38): 15858-63 (Journal)
- Registered Authors
- Goldman, Dan
- Keywords
- pyrvinium, XAV939, transgenic zebrafish, heat shock, frizzled
- MeSH Terms
-
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish/physiology
- Retina/metabolism
- Retina/physiology*
- Neuroglia/cytology
- Neuroglia/drug effects
- Neuroglia/metabolism
- Animals, Genetically Modified
- Signal Transduction*
- Cell Dedifferentiation/drug effects
- Cell Dedifferentiation/genetics
- Regeneration*
- Intercellular Signaling Peptides and Proteins/genetics
- Intercellular Signaling Peptides and Proteins/metabolism
- beta Catenin/genetics
- beta Catenin/metabolism
- Animals
- Enzyme Inhibitors/pharmacology
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- In Situ Hybridization
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Microscopy, Fluorescence
- Stem Cells/drug effects
- Stem Cells/metabolism
- Gene Knockdown Techniques
- Cell Proliferation/drug effects
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- Wnt4 Protein/genetics
- Wnt4 Protein/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Gene Expression Profiling
- Glycogen Synthase Kinase 3/antagonists & inhibitors*
- Glycogen Synthase Kinase 3/genetics
- Glycogen Synthase Kinase 3/metabolism
- PubMed
- 21911394 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Ramachandran, R., Zhao, X.F., and Goldman, D. (2011) Ascl1a/Dkk/ beta -catenin signaling pathway is necessary and glycogen synthase kinase-3 beta inhibition is sufficient for zebrafish retina regeneration. Proceedings of the National Academy of Sciences of the United States of America. 108(38):15858-63.
Abstract
Key to successful retina regeneration in zebrafish are Müller glia (MG) that respond to retinal injury by dedifferentiating into a cycling population of retinal progenitors. Although recent studies have identified several genes involved in retina regeneration, the signaling mechanisms underlying injury-dependent MG proliferation have remained elusive. Here we report that canonical Wnt signaling controls the proliferation of MG-derived retinal progenitors. We found that injury-dependent induction of Ascl1a suppressed expression of the Wnt signaling inhibitor, Dkk, and induced expression of the Wnt ligand, Wnt4a. Genetic and pharmacological inhibition of Wnt signaling suppressed injury-dependent proliferation of MG-derived progenitors. Remarkably, in the uninjured retina, glycogen synthase kinase-3β (GSK-3β) inhibition was sufficient to stimulate MG dedifferentiation and the formation of multipotent retinal progenitors that were capable of differentiating into all major retinal cell types. Importantly, Ascl1a expression was found to contribute to the multipotential character of these progenitors. Our data suggest that Wnt signaling and GSK-3β inhibition, in particular, are crucial for successful retina regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping