Stat3 defines three populations of Müller glia and is required for initiating maximal müller glia proliferation in the regenerating zebrafish retina
Open accessAbstract
We analyzed the role of Stat3, Ascl1a, and Lin28a in Müller glia reentry into the cell cycle following damage to the zebrafish retina. Immunohistochemical analysis was employed to determine the temporal and spatial expression of Stat3 and Ascl1a proteins following rod and cone photoreceptor cell apoptosis. Stat3 expression was observed in all Müller glia, whereas Ascl1a expression was restricted to only the mitotic Müller glia. Knockdown of Stat3 protein expression did not affect photoreceptor apoptosis, but significantly reduced, without abolishing, the number of proliferating Ascl1a‐positive Müller glia. Knockdown of Ascl1a protein also did not change the extent of photoreceptor apoptosis, but did yield significantly fewer Müller glia that reentered the cell cycle relative to the stat3 morphant and significantly decreased the number and intensity of Stat3‐expressing Müller glia. Finally, introduction of lin28a morpholinos resulted in decreased Müller glia expression of Stat3 and Ascl1a, significantly reducing the number of proliferating Müller glia. Thus, there are three populations of Müller glia in the light‐damaged zebrafish retina: 1) Stat3‐expressing Ascl1a‐nonexpressing nonproliferating (quiescent) Müller glia; 2) Stat3‐dependent Ascl1a‐dependent proliferating Müller glia; and 3) Stat3‐independent Ascl1a‐dependent proliferating Müller glia. Whereas Ascl1a and Lin28a are required for Müller glia proliferation, Stat3 is necessary for the maximal number of Müller glia to proliferate during regeneration of the damaged zebrafish retina. J. Comp. Neurol. 520:4294–4311, 2012. © 2012 Wiley Periodicals, Inc.
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Previous studies indicate that Mapk/Erk, Gsk3β/β-catenin and Jak/Stat3 signaling regulate Müller glia-dependent progenitor formation in the injured retina.
“Previous studies (Kassen et al., 2009; Meyers et al., 2012; Nelson et al., 2012; Ramachandran et al., 2011; Wan, 2012), along with the accompanying paper by Zhao et al., indicate that Mapk/Erk, Gsk3 β/β-catenin and Jak/Stat3 signaling regulate MG-dependent progenitor formation in the injured retina.”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Nelson et al., 2012
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“Previous studies (Kassen et al., 2009; Meyers et al., 2012; Nelson et al., 2012; Ramachandran et al., 2011; Wan, 2012), along with the accompanying paper by Zhao et al.”
BackgroundResult
- Authors
- Nelson, C. M., Gorsuch, R. A., Bailey, T. J., Ackerman, K. M., Kassen, S. C., & Hyde, D. R.
- Affiliations
- University of Notre Dame (US)
- Corresponding author
- Hyde, David R.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2012-10-20
- Volume
- 520
- Issue
- 18
- Pages
- 4294-4311
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- PMC
- PMC3478445
- OpenAlex
- W2104008103
- Cited by
- 123
- References
- 46
- Citations by year
- 2026: 11 · 2025: 3 · 2024: 9 · 2023: 11 · 2022: 10 · 2021: 11 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 7 · 2015: 8 · 2014: 10 · 2013: 11
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (R01-RY018417)
- National Eye Institute (R01EY018417)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- STAT3, Müller cells, retinal regeneration, LIN28A, cell cycle re-entry, photoreceptor apoptosis, zebrafish retina, morpholino knockdown
- MeSH terms
- Actins, Adaptation, Ocular, Animals, Cell Count, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Light, Neuroglia, Retina, Retinal Diseases, RNA, Messenger, Transcription Factors, Zebrafish, Proliferating Cell Nuclear Antigen, Zebrafish Proteins, Animals, Genetically Modified, Cell Proliferation, Green Fluorescent Proteins, STAT3 Transcription Factor, Basic Helix-Loop-Helix Proteins, Neurogenesis
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