PUBLICATION
HB-EGF Is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration
- Authors
- Wan, J., Ramachandran, R., and Goldman, D.
- ID
- ZDB-PUB-120223-1
- Date
- 2012
- Source
- Developmental Cell 22(2): 334-347 (Journal)
- Registered Authors
- Goldman, Dan
- Keywords
- none
- MeSH Terms
-
- Blotting, Western
- Cell Differentiation*
- Wnt Proteins/genetics
- Wnt Proteins/metabolism
- Real-Time Polymerase Chain Reaction
- Epidermal Growth Factor/pharmacology
- Receptors, Notch/genetics
- Receptors, Notch/metabolism
- beta Catenin/genetics
- beta Catenin/metabolism
- Signal Transduction
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- Heparin-binding EGF-like Growth Factor
- Multipotent Stem Cells/cytology
- Multipotent Stem Cells/metabolism
- Retina/cytology*
- Retina/metabolism*
- Immunoenzyme Techniques
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Zebrafish
- Oligonucleotides, Antisense/pharmacology
- Mitogen-Activated Protein Kinases/genetics
- Mitogen-Activated Protein Kinases/metabolism
- Animals
- RNA, Messenger/genetics
- Regeneration*
- Neuroglia/cytology*
- Neuroglia/metabolism*
- Intercellular Signaling Peptides and Proteins/chemistry
- Intercellular Signaling Peptides and Proteins/genetics
- Intercellular Signaling Peptides and Proteins/metabolism*
- In Situ Hybridization
- PubMed
- 22340497 Full text @ Dev. Cell
Citation
Wan, J., Ramachandran, R., and Goldman, D. (2012) HB-EGF Is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration. Developmental Cell. 22(2):334-347.
Abstract
Müller glia (MG) dedifferentiation into a cycling population of multipotent progenitors is crucial to zebrafish retina regeneration. The mechanisms underlying MG dedifferentiation are unknown. Here we report that heparin-binding epidermal-like growth factor (HB-EGF) is rapidly induced in MG residing at the injury site and that pro-HB-EGF ectodomain shedding is necessary for retina regeneration. Remarkably, HB-EGF stimulates the formation of multipotent MG-derived progenitors in the uninjured retina. We show that HB-EGF mediates its effects via an EGFR/MAPK signal transduction cascade that regulates the expression of regeneration-associated genes, like ascl1a and pax6b. We also uncover an HB-EGF/Ascl1a/Notch/hb-egfa- signaling loop that helps define the zone of injury-responsive MG. Finally, we show that HB-EGF acts upstream of the Wnt/β-catenin-signaling cascade that controls progenitor proliferation. These data provide a link between extracellular signaling and regeneration-associated gene expression in the injured retina and suggest strategies for stimulating retina regeneration in mammals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping