Cited by 647Retinal Development and DisordersNeurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene Regulation

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Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells

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Bernardos, R. L., Barthel, L. K., Meyers, J. R., Raymond, P. A.·2007·Journal of Neuroscience

DOI 10.1523/jneurosci.1624-07.2007PMC PMC6672216

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Abstract

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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Authors: Bernardos, R. L., Barthel, L. K., Meyers, J. R., & Raymond, P. A.
Affiliations: University of Michigan (US)
ORCID: Bernardos, R. L.
Meyers, J. R.
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
DOI: 10.1523/jneurosci.1624-07.2007
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

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Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells

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