The DOI matches its Crossref record; 58 of the 60 references it cites were found in a registry or an index.
Wnt Signaling Promotes Regeneration in the Retina of Adult Mammals
Open accessAbstract
Regeneration in the mammalian CNS is severely limited. Unlike in the chick, current models hold that retinal neurons are never regenerated. Previously we demonstrated that, in the adult mammalian retina, Müller glia dedifferentiate and produce retinal cells, including photoreceptors, after acute neurotoxic injury in vivo . However, the number of newly generated retinal neurons is very limited. Here we demonstrate that Wnt (wingless-type MMTV integration site family)/β-catenin signaling promotes proliferation of Müller glia-derived retinal progenitors and neural regeneration after damage or during degeneration. Wnt3a treatment increases proliferation of dedifferentiated Müller glia >20-fold in the photoreceptor-damaged retina. Supplementation with retinoic acid or valproic acid induces differentiation of these cells primarily into Crx (cone rod homeobox)-positive and rhodopsin-positive photoreceptors. Notably, injury induces nuclear accumulation of β-catenin, cyclin D1 upregulation, and Wnt/β-catenin reporter activity. Activation of Wnt signaling by glycogen synthase kinase-3β inhibitors promotes retinal regeneration, and, conversely, inhibition of the signaling attenuates regeneration. This Wnt3a-mediated regeneration of retinal cells also occurs in rd mice, a model of retinal degeneration. These results provide evidence that Wnt/β-catenin signaling contributes to CNS regeneration in the adult mammal.
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“they only exhibit a limited regenerative potential under special conditions”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Osakada et al., 2007
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“It is interesting that in mammals, β-catenin has been associated with a very limited amount of MG proliferation while pStat3 has been associated with injury-induced gliosis (Osakada et al., 2007; Peterson et al., 2000; Rhee et al., 2013; Xue et al., 2011).”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Osakada et al., 2007
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Citations
Cites
Gage, F. H. (2000) · Science · doi:10.1126/science.287.5457.1433 · Cited by 4,786
Wnt signalling in stem cells and cancer
Reya, T., & Clevers, H. (2005) · Nature · doi:10.1038/nature03319 · Cited by 3,666
β-Catenin regulates expression of cyclin D1 in colon carcinoma cells
Tetsu, O., & McCormick, F. (1999) · Nature · doi:10.1038/18884 · Cited by 3,601
Polakis, P. (2000) · Genes & Development · doi:10.1101/gad.14.15.1837 · Cited by 3,183
Functional neurogenesis in the adult hippocampus
van Praag, H., Schinder, A. F., Christie, B. R., Toni, N., Palmer, T. D., & Gage, F. H. (2002) · Nature · doi:10.1038/4151030a · Cited by 2,853
Neuronal replacement from endogenous precursors in the adult brain after stroke
Arvidsson, A., Collin, T., Kirik, D., Kokaia, Z., & Lindvall, O. (2002) · Nature Medicine · doi:10.1038/nm747 · Cited by 2,799
The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway
Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R., & Ben-Ze’ev, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5522 · Cited by 2,230
A role for Wnt signalling in self-renewal of haematopoietic stem cells
Reya, T., Duncan, A. W., Ailles, L., Domen, J., Scherer, D. C., Willert, K., Hintz, L., Nusse, R., & Weissman, I. L. (2003) · Nature · doi:10.1038/nature01593 · Cited by 2,159
MECHANISMS OF WNT SIGNALING IN DEVELOPMENT
Wodarz, A., & Nusse, R. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.59 · Cited by 2,030
ADULT NEUROGENESIS IN THE MAMMALIAN CENTRAL NERVOUS SYSTEM
Ming, G., & Song, H. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.051804.101459 · Cited by 1,891
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Self-citationStem Cells in the Developing and Adult Nervous System
Osakada, F., & Takahashi, M. (2013) · Springer eBooks · doi:10.1007/978-94-007-5690-8_5
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Blastocyst-like Structures in the Peripheral Retina of Young Adult Beagles
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Toward Regeneration of Retinal Function Using Pluripotent Stem Cells
Osakada, F., & Takahashi, M. (2011) · Humana Press eBooks · doi:10.1007/978-1-61779-225-0_13
Self-citationYakoubi, W. E. (2012) · theses.fr (ABES) · doi:10.70675/c7f12aa8zb750z4a9ez8b33za3e1f7ab1093
蒋池, か. (2020) · Institutional Repositories DataBase (IRDB) · doi:10.20780/00032720
Retinal ciliopathies in Huntington's and SCA7 disorders
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Proliferative Capacity and Neural Lineage Commitment of Müller Glia in the Adult Human RetinaPreprint
Magda, D. P., Tyler, T., Gerendás, L., Kilin, F., Csorba, A., György, B., Picelli, S., Nagy, Z. Z., & Szabó, A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.27.717633
FGF Signaling Potentiates Müller Glia for Mammalian Retinal RegenerationPreprint
Makrides, N., Wu, Y., Kissner, M., Peregrin, J., Hannan, A., & Zhang, X. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.26.731914
Reprogramming Mammal Müller Glial Cells for Retinal Neuroregeneration
Huang, L. J., Yao, E., Yang, M., & Chen, D. F. (2026) · American Journal Of Pathology · doi:10.1016/j.ajpath.2026.06.006
Metadata
- Authors
- Osakada, F., Ooto, S., Akagi, T., Mandai, M., Akaike, A., & Takahashi, M.
- Affiliations
- RIKEN (JP)
- Kyoto University (JP)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-04-11
- Volume
- 27
- Issue
- 15
- Pages
- 4210-4219
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672527
- OpenAlex
- W1967448020
- Cited by
- 322
- References
- 60
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 7 · 2023: 10 · 2022: 19 · 2021: 13 · 2020: 15 · 2019: 13 · 2018: 14 · 2017: 15 · 2016: 18 · 2015: 24 · 2014: 26 · 2013: 25 · 2012: 19
- FWCI
- 10.59
- 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
- Japan Society for the Promotion of Science
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- Wnt/β-catenin signaling, retinal regeneration, retinal progenitor cells, photoreceptor regeneration, Wnt3a, retinoic acid, valproic acid, CRX, rhodopsin, glycogen synthase kinase-3β, cyclin D1, retinal degeneration, central nervous system regeneration
- MeSH terms
- Animals, Macaca fascicularis, Male, Mice, Transgenic, Nerve Regeneration, Organ Culture Techniques, Retina, Signal Transduction, Wnt Proteins, Mice, Rats, Wnt3 Protein, Wnt3A Protein
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