title: Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration.
abstract: 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.
authors.affiliation: The Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Wan
authors.affiliation: The Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhao
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Vojtek
authors.affiliation: The Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: neuroman@umich.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Goldman
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D012160:Retina / Q000293:injuries / Q000378:metabolism* / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D050796:STAT3 Transcription Factor; D029961:Zebrafish Proteins; D051176:beta Catenin; C494089:stat3 protein, zebrafish