Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration

Cell Rep. 2014 Oct 9;9(1):285-297. doi: 10.1016/j.celrep.2014.08.048. Epub 2014 Sep 25.


Müller glia (MG) in the zebrafish retina respond to retinal injury by generating multipotent progenitors for retinal repair. Here, we show that Insulin, Igf-1, and fibroblast growth factor (FGF) signaling components are necessary for retina regeneration. Interestingly, these factors synergize with each other and with heparin-binding EGF-like growth factor (HB-EGF) and cytokines to stimulate MG to generate multipotent progenitors in the uninjured retina. These factors act by stimulating a core set of signaling cascades (Mapk/Erk, phosphatidylinositol 3-kinase [PI3K], β-catenin, and pStat3) that are also shared with retinal injury and exhibit a remarkable amount of crosstalk. Our studies suggest that MG both produce and respond to factors that stimulate MG reprogramming and proliferation following retinal injury. The identification of a core set of regeneration-associated signaling pathways required for MG reprogramming not only furthers our understanding of retina regeneration in fish but also suggests targets for enhancing regeneration in mammals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation / physiology
  • Cytokines / metabolism*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Nerve Regeneration / physiology*
  • Retina / injuries
  • Retina / metabolism*
  • Retina / physiology*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins / metabolism*
  • beta Catenin / metabolism*


  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • STAT3 Transcription Factor
  • Zebrafish Proteins
  • beta Catenin
  • stat3 protein, zebrafish