The Proneural Basic Helix-Loop-Helix Gene Ascl1a Is Required for Retina Regeneration
Open accessAbstract
Unlike mammals, teleost fish can regenerate an injured retina, restoring lost visual function. Little is known of the molecular events that underlie retina regeneration. We previously found that in zebrafish, retinal injury stimulates Müller glia to generate multipotent α 1-tubulin (α 1T ) and pax6 -expressing progenitors for retinal repair. Here, we report the identification of a critical E-box in the α 1T promoter that mediates transactivation by achaete-scute complex-like 1a (ascl1a) during retina regeneration. More importantly, we show that ascl1a is essential for retina regeneration. Within 4 h after retinal injury, ascl1a is induced in Müller glia. Knockdown of ascl1a blocks the induction of α 1T and pax6 as well as Müller glial proliferation, consequently preventing the generation of retinal progenitors and their differentiated progeny. These data suggest ascl1a is required to convert quiescent Müller glia into actively dividing retinal progenitors, and that ascl1a is a key regulator in initiating retina regeneration.
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Ascl1a is required for Müller glia dedifferentiation and retinal regeneration through activation of a Lin-28/let-7 pathway.
“Ascl1a is necessary for MG dedifferentiation and retina regeneration by activating a Lin-28/let-7 signaling pathway”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Fausett et al., 2008
Ascl1 is an essential regeneration-associated gene in zebrafish.
“Indeed, EGF stimulation of the injured mouse retina did not induce Ascl1 gene expression (Karl et al., 2008), which is an essential regeneration-associated gene in zebrafish (Fausett et al., 2008; Ramachandran et al., 2010a).”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Fausett et al., 2008
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 et al., 2008
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- Authors
- Fausett, B. V., Gumerson, J. D., & Goldman, D.
- Affiliations
- University of Michigan (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-01-30
- Volume
- 28
- Issue
- 5
- Pages
- 1109-1117
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2800945
- OpenAlex
- W2059560084
- Cited by
- 251
- References
- 34
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 13 · 2023: 29 · 2022: 15 · 2021: 20 · 2020: 15 · 2019: 15 · 2018: 6 · 2017: 9 · 2016: 9 · 2015: 10 · 2014: 15 · 2013: 17 · 2012: 8
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Michigan
- National Institutes of Health
- National Eye Institute (R01EY018132)
- 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
- retinal regeneration, Müller cells, Pax6, E-box promoter, retinal progenitor cells, zebrafish, retinal damage, glial cell proliferation
- MeSH terms
- Animals, Cell Line, Cytoskeletal Proteins, Neuroglia, Neurons, Promoter Regions, Genetic, Regeneration, Retina, Zebrafish, Signal Transduction, Helix-Loop-Helix Motifs, Zebrafish Proteins, Animals, Genetically Modified
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