A Role for 1 Tubulin-Expressing Muller Glia in Regeneration of the Injured Zebrafish Retina
Open accessAbstract
Alpha1 tubulin (alpha1T) is a neuron-specific microtubule protein whose expression is induced in the developing and regenerating CNS. In the adult CNS, alpha1T expression remains high in neural progenitors. Transgenic zebrafish harboring a 1.7 kb alpha1T promoter fragment along with the first exon and intron express the transgene in a manner that recapitulates expression of the endogenous gene. We recently showed that this promoter mediates gene induction in retinal ganglion cells during optic nerve regeneration and in a subset of Müller glia that proliferate after retinal injury (Senut et al., 2004). To further characterize these Müller glia, we generated transgenic fish harboring an alpha1T promoter fragment that is specifically induced in these cells after retinal damage. Transgene expression, bromodeoxyuridine (BrdU) labeling, and stem cell marker expression suggested that alpha1T-expressing Müller glia dedifferentiate and become multipotent in response to injury. In addition, green fluorescent protein and BrdU-mediated lineage tracing combined with retinal gene expression analysis indicated that alpha1T-expressing Müller glia were capable of generating retinal neurons and glia. These data strongly suggest alpha1T-expressing Müller glia dedifferentiate and mediate regeneration of the injured zebrafish retina.
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The zebrafish retina is a useful model for uncovering how stem cells activate and astrocytes dedifferentiate because it regenerates robustly after injury and this regeneration requires Müller glia dedifferentiation.
“The zebrafish retina is an important model for revealing these mechanisms since the retina is able to mount a robust regenerative response following injury and this response is dependent on the dedifferentiation of Müller glia (MG)”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Fausett and Goldman, 2006
The 1016 tuba1a:gfp transgenic fish report Müller glia dedifferentiation and proliferation by restricting GFP to Müller glia-derived progenitors.
“1016 tuba1a:gfp transgenic fish that report MG dedifferentiation and proliferation by restricting GFP expression to MG-derived progenitors”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Fausett and Goldman, 2006
Müller glia mount a regenerative response regardless of whether injury affects only photoreceptors, inner retinal neurons, or all retinal cell types.
“It is interesting that MG elicit a regenerative response regardless if injury affects only photoreceptors, inner retinal neurons or all retinal cell types (Fausett and Goldman, 2006; Fimbel et al., 2007; Montgomery et al., 2010; Vihtelic and Hyde, 2000).”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Fausett and Goldman, 2006
Essentially all proliferating cells in the inner nuclear layer after needle poke injury are Müller glia-derived progenitors.
“Furthermore, those studies showed that essentially all the proliferating cells in the inner nuclear layer (INL) were MG-derived progenitors (Fausett and Goldman, 2006).”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Fausett and Goldman, 2006
Müller glia are key to successful retina regeneration.
“Key to successful retina regeneration are Müller glia (MG), the major glial cell-type in the retina (Bernardos et al., 2007; Fausett and Goldman, 2006; Fimbel et al., 2007).”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Fausett and Goldman, 2006
After needle poke injury, Müller glia at the injury site proliferate and generate multipotent progenitors for retinal repair.
“We previously demonstrated that following a needle poke injury, MG at the injury site proliferate and generate multipotent progenitors for retinal repair (Fausett and Goldman, 2006).”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Fausett and Goldman, 2006
Zebrafish Müller glia respond to retinal injury by producing multipotent progenitors that repair the retina.
“Müller glia (MG) in the zebrafish retina respond to retinal injury by generating multipotent progenitors for retinal repair.”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Fausett and Goldman, 2006
Müller glia mount a similar response to many different injuries, whether the injuries are restricted to specific cell types or more widespread.
“It is interesting that MG mount a similar response to a variety of injuries regardless if these injuries are restricted to specific cell types or more widespread (Fausett and Goldman, 2006; Fimbel et al., 2007; Montgomery et al., 2010; Vihtelic and Hyde, 2000).”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Fausett and Goldman, 2006
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- Authors
- Fausett, B. V., & Goldman, D.
- Affiliations
- University of Michigan (US)
- ORCID
- Goldman, D.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-06-07
- Volume
- 26
- Issue
- 23
- Pages
- 6303-6313
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6675181
- OpenAlex
- W2093315874
- Cited by
- 435
- References
- 44
- Citations by year
- 2026: 22 · 2025: 17 · 2024: 16 · 2023: 31 · 2022: 30 · 2021: 28 · 2020: 25 · 2019: 25 · 2018: 20 · 2017: 26 · 2016: 24 · 2015: 22 · 2014: 22 · 2013: 26 · 2012: 20
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michigan Economic Development Corporation
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- Müller cells, retinal regeneration, retinal damage, zebrafish, multipotency, retinal ganglion cells, optic nerve regeneration, lineage tracing, retinal progenitor cells, transgenic fish
- MeSH terms
- Animals, Cell Differentiation, Neuroglia, Neurons, Promoter Regions, Genetic, Regeneration, Retina, Tubulin, Wounds and Injuries, Zebrafish, Gene Expression, Transgenes, Animals, Genetically Modified, Multipotent Stem Cells, Cell Proliferation
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