PUBLICATION

Opposing Actions of Fgf8a on Notch Signaling Distinguish Two Muller Glial Cell Populations that Contribute to Retina Growth and Regeneration

Authors
Wan, J., Goldman, D.
ID
ZDB-PUB-170427-2
Date
2017
Source
Cell Reports   19: 849-862 (Journal)
Registered Authors
Goldman, Dan, Wang,Jin
Keywords
Fgf8, Muller glia, Notch, regeneration, reprogramming, retina, stem cell, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified/metabolism
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Ependymoglial Cells/cytology
  • Ependymoglial Cells/metabolism
  • Fibroblast Growth Factors/antagonists & inhibitors
  • Fibroblast Growth Factors/genetics
  • Fibroblast Growth Factors/metabolism*
  • In Situ Hybridization, Fluorescence
  • Microscopy, Fluorescence
  • Morpholinos/metabolism
  • Neuroglia/cytology
  • Neuroglia/metabolism
  • RNA Interference
  • Receptors, Notch/metabolism*
  • Regeneration
  • Retina/pathology
  • Retina/physiology*
  • Signal Transduction
  • Temperature
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
28445734 Full text @ Cell Rep.
Abstract
The teleost retina grows throughout life and exhibits a robust regenerative response following injury. Critical to both these events are Muller glia (or, Muller glial cells; MGs), which produce progenitors for retinal growth and repair. We report that Fgf8a may be an MG niche factor that acts through Notch signaling to regulate spontaneous and injury-dependent MG proliferation. Remarkably, forced Fgf8a expression inhibits Notch signaling and stimulates MG proliferation in young tissue but increases Notch signaling and suppresses MG proliferation in older tissue. Furthermore, cessation of Fgf8a signaling enhances MG proliferation in both young and old retinal tissue. Our study suggests that multiple MG populations contribute to retinal growth and regeneration, and it reveals a previously unappreciated role for Fgf8a and Notch signaling in regulating MG quiescence, activation, and proliferation.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping