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Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells
Open accessAbstract
Neuronal progenitors in the mammalian brain derive from radial glia or specialized astrocytes. In developing neural retina, radial glia-like Müller cells are generated late in neurogenesis and are not considered to be neuronal progenitors, but they do proliferate after injury and can express neuronal markers, suggesting a latent neurogenic capacity. To examine the neurogenic capacity of retinal glial cells, we used lineage tracing in transgenic zebrafish with a glial-specific promoter (gfap, for glial fibrillary acid protein) driving green fluorescent protein in differentiated Müller glia. We found that all Müller glia in the zebrafish retina express low levels of the multipotent progenitor marker Pax6 (paired box gene 6), and they proliferate at a low frequency in the intact, uninjured retina. Müller glia-derived progenitors express Crx (cone rod homeobox) and are late retinal progenitors that generate the rod photoreceptor lineage in the postembryonic retina. These Müller glia-derived progenitors also remain competent to produce earlier neuronal lineages, in that they respond to loss of cone photoreceptors by specifically regenerating the missing neurons. We conclude that zebrafish Müller glia function as multipotent retinal stem cells that generate retinal neurons by homeostatic and regenerative developmental mechanisms.
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“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 Bernardos et al., 2007
In the citing paper
“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 Bernardos et al., 2007
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Metadata
- Authors
- Bernardos, R. L., Barthel, L. K., Meyers, J. R., & Raymond, P. A.
- Affiliations
- University of Michigan (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-06-27
- Volume
- 27
- Issue
- 26
- Pages
- 7028-7040
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672216
- OpenAlex
- W2016508121
- Cited by
- 647
- References
- 60
- Citations by year
- 2026: 28 · 2025: 22 · 2024: 32 · 2023: 40 · 2022: 39 · 2021: 38 · 2020: 38 · 2019: 33 · 2018: 31 · 2017: 27 · 2016: 36 · 2015: 32 · 2014: 33 · 2013: 45 · 2012: 33
- FWCI
- 13.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (R01EY004318, F32EY017251)
- National Institute of Neurological Disorders and Stroke (F31NS047909)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Müller cells, retinal stem cells, neuronal precursors, retinal neurogenesis, zebrafish retina, Pax6, CRX, rod photoreceptors, photoreceptor regeneration, glial fibrillary acidic protein, lineage tracing, retinal homeostasis, multipotent progenitors
- MeSH terms
- Aging, Animals, Cell Differentiation, Homeostasis, Neuroglia, Neurons, Regeneration, Retina, Species Specificity, Stem Cells, Zebrafish, Cell Lineage
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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