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
-
- In Situ Hybridization
- Mitogen-Activated Protein Kinases/genetics
- Mitogen-Activated Protein Kinases/metabolism
- RNA, Messenger/genetics
- Oligonucleotides, Antisense/pharmacology
- PubMed
- 22340497 Full text @ Dev. Cell
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.
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