PUBLICATION

Characterization of the pleiotropic roles of Sonic Hedgehog during retinal regeneration in adult zebrafish

Authors
Thomas, J.L., Morgan, G.W., Dolinski, K.M., Thummel, R.
ID
ZDB-PUB-171017-15
Date
2017
Source
Experimental Eye Research   166: 106-115 (Journal)
Registered Authors
Thomas, Jennifer, Thummel, Ryan
Keywords
Cyclopamine, Müller glia, Regeneration, Retina, Sonic Hedgehog, Zebrafish
MeSH Terms
  • Animals
  • Cell Differentiation/physiology
  • Cell Proliferation/physiology
  • Ependymoglial Cells
  • Hedgehog Proteins/metabolism
  • Hedgehog Proteins/physiology*
  • Regeneration/physiology*
  • Retina/metabolism
  • Retina/physiology*
  • Retinal Neurons/metabolism
  • Signal Transduction/physiology*
  • Zebrafish
PubMed
29030175 Full text @ Exp. Eye. Res.
Abstract
In contrast to the mammalian retina, the zebrafish retina possesses the ability to regenerate. This is primarily accomplished through Müller glial cells, which, upon damage, re-enter the cell cycle to form retinal progenitors. The progenitors continue to proliferate as they migrate to the area of damage and ultimately differentiate into new neurons. The purpose of this study was to characterize the expression and function of Sonic Hedgehog (Shh) during regeneration of the adult zebrafish retina. Expression profiling of Shh pathway genes showed a significant upregulation of expression associated with stages of progenitor proliferation and neuronal differentiation. Activation of Shh signaling during early stages of retinal regeneration using intraocular injections of the recombinant human SHH (SHH-N) resulted in increased Müller cell gliosis, proliferation, and neuroprotection of damaged retinal neurons. Continued activation of Shh resulted in a greater number of differentiated amacrine and ganglion cells in the fully regenerated retina. Conversely, inhibition of Shh signaling using intraocular injections of cyclopamine resulted in decreased Müller glial cell proliferation and a fewer number of regenerated amacrine and ganglion cells. These data suggest that Shh signaling plays pleiotropic roles in proliferation and differentiation during adult zebrafish retinal regeneration.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping