PUBLICATION

Leptin and IL-6 Family Cytokines Synergize to Stimulate Müller Glia Reprogramming and Retina Regeneration

Authors
Zhao, X.F., Wan, J., Powell, C., Ramachandran, R., Myers, M.G., Goldman, D.
ID
ZDB-PUB-140930-9
Date
2014
Source
Cell Reports   9(1): 272-84 (Journal)
Registered Authors
Goldman, Dan
Keywords
none
MeSH Terms
  • Interleukin-6/metabolism*
  • Neural Stem Cells/metabolism
  • Leptin/metabolism*
  • Zebrafish Proteins/metabolism
  • STAT3 Transcription Factor/metabolism
  • Signal Transduction
  • Janus Kinases/metabolism
  • Animals, Genetically Modified
  • Nerve Regeneration/physiology*
  • Drosophila Proteins/metabolism
  • Animals
  • Retina/injuries
  • Retina/metabolism
  • Retina/physiology*
  • Transcription Factors/metabolism
  • Cellular Reprogramming/physiology*
  • Zebrafish
  • Neuroglia/cytology
  • Neuroglia/metabolism
  • Neuroglia/physiology*
(all 20)
PubMed
25263554 Full text @ Cell Rep.
Abstract
Unlike mammals, zebrafish can regenerate a damaged retina. This remarkable regenerative response is mediated by Müller glia (MG) that undergo a reprogramming event that drives their proliferation and the generation of multipotent progenitors for retinal repair. The mechanisms that drive MG reprogramming are poorly understood. Here, we report that Leptin and Gp130-coupled receptors, acting via a Jak/Stat signaling pathway, stimulate MG reprogramming and progenitor formation in the injured retina. Importantly, we find that ascl1a gene expression, which drives MG reprogramming in fish and mammals, is regulated in a Jak/Stat-dependent manner and requires consensus Stat-binding sites for injury-dependent activation. Finally, we identify cytokines that are induced by retinal injury and exhibit a remarkable synergy in their ability to activate Jak/Stat signaling and MG reprogramming in the uninjured retina. Our study not only furthers our understanding of retina regeneration in zebrafish but also suggests new strategies for awakening retina regeneration in mammals.
Genes / Markers
Figures
Figure Gallery (14 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mi4TgTransgenic Insertion
    mi30TgTransgenic Insertion
      mi31TgTransgenic Insertion
        mi32TgTransgenic Insertion
          mi33TgTransgenic Insertion
            mi35TgTransgenic Insertion
              mi37TgTransgenic Insertion
                nt11TgTransgenic Insertion
                  1 - 8 of 8
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                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  il6stMO1-il6stMRPHLNO
                  leprMO2-leprMRPHLNO
                  1 - 2 of 2
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                  Fish
                  Antibodies
                  Name Type Antigen Genes Isotypes Host Organism
                  Ab1-stat3monoclonalIgG1Mouse
                  Ab-4C4monoclonal
                    IgG1Mouse
                    1 - 2 of 2
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                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    EGFPEFGEGFP
                    GFPEFGGFP
                    1 - 2 of 2
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                    Mapping
                    No data available