Retinal regeneration in adult zebrafish requires regulation of TGFβ signaling

Glia. 2013 Oct;61(10):1687-97. doi: 10.1002/glia.22549. Epub 2013 Aug 5.

Abstract

Müller glia are the resident radial glia in the vertebrate retina. The response of mammalian Müller glia to retinal damage often results in a glial scar and no functional replacement of lost neurons. Adult zebrafish Müller glia, in contrast, are considered tissue-specific stem cells that can self-renew and generate neurogenic progenitors to regenerate all retinal neurons after damage. Here, we demonstrate that regulation of TGFβ signaling by the corepressors Tgif1 and Six3b is critical for the proliferative response to photoreceptor destruction in the adult zebrafish retina. When function of these corepressors is disrupted, Müller glia and their progeny proliferate less, leading to a significant reduction in photoreceptor regeneration. Tgif1 expression and regulation of TGFβ signaling are implicated in the function of several types of stem cells, but this is the first demonstration that this regulatory network is necessary for regeneration of neurons.

Keywords: Müller glia; photoreceptor; six3b; stem cell; tgif1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Proliferation
  • Disease Models, Animal
  • Ependymoglial Cells / metabolism*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Eye Proteins / genetics
  • Gliosis / genetics
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Mutation / genetics
  • Nerve Regeneration / physiology*
  • Nerve Tissue Proteins / genetics
  • Photic Stimulation / adverse effects
  • Retina / pathology
  • Retinal Degeneration / etiology
  • Retinal Degeneration / pathology*
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation / genetics
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Extracellular Matrix Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Sine oculis homeobox homolog 3 protein
  • Transforming Growth Factor beta
  • Zebrafish Proteins
  • Green Fluorescent Proteins
  • betaIG-H3 protein