Retinal regeneration in adult zebrafish requires regulation of TGFβ signaling
- Authors
- Lenkowski, J.R., Qin, Z., Sifuentes, C.J., Thummel, R., Soto, C.M., Moens, C.B., Raymond, P.A..
- ID
- ZDB-PUB-130830-2
- Date
- 2013
- Source
- Glia 61(10): 1687-1697 (Journal)
- Registered Authors
- Moens, Cecilia, Raymond, Pamela, Thummel, Ryan
- Keywords
- Muller glia, photoreceptor, tgif1, six3b, stem cell
- MeSH Terms
-
- Animals, Genetically Modified
- Photic Stimulation/adverse effects
- Up-Regulation/genetics
- Animals
- Mutation/genetics
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Gliosis/genetics
- Ependymoglial Cells/metabolism*
- Nerve Tissue Proteins/genetics
- Signal Transduction/physiology*
- Transforming Growth Factor beta/genetics
- Transforming Growth Factor beta/metabolism*
- Cell Proliferation
- Disease Models, Animal
- Nerve Regeneration/physiology*
- Extracellular Matrix Proteins/genetics
- Extracellular Matrix Proteins/metabolism
- Homeodomain Proteins/genetics
- Retinal Degeneration/etiology
- Retinal Degeneration/pathology*
- Eye Proteins/genetics
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Retina/pathology
- PubMed
- 23918319 Full text @ Glia
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.