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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Wnt signalling regulates adult hippocampal neurogenesis
Lie, D. C., Colamarino, S. A., Song, H., Désiré, L., Mira, H., Consiglio, A., Lein, E. S., Jessberger, S., Lansford, H., Dearie, A. R., et al. (2005) · Nature · doi:10.1038/nature04108 · Cited by 1,544
Neurogenesis in Adult Subventricular Zone
Álvarez-Buylla, A., & García‐Verdugo, J. M. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00629.2002 · Cited by 1,502
Nakatomi, H., Kuriu, T., Okabe, S., Yamamoto, S.-I., Hatano, O., Kawahara, N., Tamura, A., Kirino, T., & Nakafuku, M. (2002) · Cell · doi:10.1016/s0092-8674(02)00862-0 · Cited by 1,418
Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus
Schmidt-Hieber, C., Jonas, P., & Bischofberger, J. (2004) · Nature · doi:10.1038/nature02553 · Cited by 1,292
Induction of neurogenesis in the neocortex of adult mice
Magavi, S. S. P., Leavitt, B. R., & Macklis, J. D. (2000) · Nature · doi:10.1038/35016083 · Cited by 1,217
Kuhn, H. G., Winkler, J., Kempermann, G., Thal, L. J., & Gage, F. H. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-15-05820.1997 · Cited by 1,214
Retinal Stem Cells in the Adult Mammalian Eye
Tropepe, V., Coles, B. L. K., Chiasson, B. J., Horsford, D. J., Elia, A., McInnes, R. R., & van der Kooy, D. (2000) · Science · doi:10.1126/science.287.5460.2032 · Cited by 1,090
Imitola, J., Raddassi, K., Park, K. I., Müeller, F.-J., Nieto, M., Teng, Y. D., Frenkel, D., Li, J., Sidman, R. L., Walsh, C. A., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408258102 · Cited by 1,089
DasGupta, R., & Fuchs, E. V. (1999) · Development · doi:10.1242/dev.126.20.4557 · Cited by 995
Coghlan, M. P., Culbert, A. A., Cross, D. A. E., Corcoran, S. L., Yates, J. W., Pearce, N. J., Rausch, O., Murphy, G. J., Carter, P. S., Cox, L. R., et al. (2000) · Chemistry & Biology · doi:10.1016/s1074-5521(00)00025-9 · Cited by 906
Furukawa, T., Morrow, E. M., & Cepko, C. L. (1997) · Cell · doi:10.1016/s0092-8674(00)80439-0 · Cited by 901
Rickman, C. B., Li, T., Danciger, M., Baxter, L. C., Applebury, M., & Farber, D. B. (1990) · Nature · doi:10.1038/347677a0 · Cited by 852
GSK3 inhibitors: development and therapeutic potential
Cohen, P., & Goedert, M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1415 · Cited by 801
Hsieh, J., Nakashima, K., Kuwabara, T., Mejia, E., & Gage, F. H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407643101 · Cited by 729
Chen, S., Wang, Q., Nie, Z., Sun, H., Lennon, G. G., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., & Zack, D. J. (1997) · Neuron · doi:10.1016/s0896-6273(00)80394-3 · Cited by 712
Axonal Remodeling and Synaptic Differentiation in the Cerebellum Is Regulated by WNT-7a Signaling
Hall, A. C., Lucas, F. R., & Salinas, P. C. (2000) · Cell · doi:10.1016/s0092-8674(00)80689-3 · Cited by 699
McLaughlin, M. E., Sandberg, M. A., Berson, E. L., & Dryja, T. P. (1993) · Nature Genetics · doi:10.1038/ng0693-130 · Cited by 602
Genomic Analysis of Mouse Retinal Development
Blackshaw, S., Harpavat, S., Trimarchi, J. M., Cai, L., Huang, H., Kuo, W. P., Weber, G. M., Lee, K., Fraioli, R. E., Cho, S., et al. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020247 · Cited by 586
Müller glia are a potential source of neural regeneration in the postnatal chicken retina
Fischer, A. J., & Reh, T. A. (2001) · Nature Neuroscience · doi:10.1038/85090 · Cited by 579
Bhat, R. V., Xue, Y., von Berg, S., Hellberg, S., Ormö, M., Nilsson, Y., Radesäter, A., Jerning, E., Markgren, P.-O., Borgegård, T., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306268200 · Cited by 568
Anterior-Posterior Guidance of Commissural Axons by Wnt-Frizzled Signaling
Lyuksyutova, A. I., Lu, C.-C., Milanesio, N., King, L. A., Guo, N., Wang, Y., Nathans, J., Tessier‐Lavigne, M., & Zou, Y. (2003) · Science · doi:10.1126/science.1089610 · Cited by 557
Kiecker, C. M., & Niehrs, C. (2001) · Development · doi:10.1242/dev.128.21.4189 · Cited by 515
Corepressor-Dependent Silencing of Chromosomal Regions Encoding Neuronal Genes
Lunyak, V. V., Burgess, R., Prefontaine, G. G., Nelson, C., Sze, S.-H., Chenoweth, J., Schwartz, P., Pevzner, P. A., Glass, C., Mandel, G., et al. (2002) · Science · doi:10.1126/science.1076469 · Cited by 472
Potential for neural regeneration after neurotoxic injury in the adult mammalian retina
Ooto, S., Akagi, T., Kageyama, R., Akita, J., Mandai, M., Honda, Y., & Takahashi, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402129101 · Cited by 454
Self-citationIdentification of Neural Progenitors in the Adult Mammalian Eye
Ahmad, I., Tang, L., & Pham, H. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2473 · Cited by 433
Teng, Y. D., Frenkel, D., Nieto, M., Müeller, F.-J., Park, K. I., Raddassi, K., Imitola, J., Li, J., Sidman, R. L., Walsh, C. A., et al. (2004) · Cited by 421
Generating neuronal diversity in the retina: one for nearly all
Marquardt, T., & Gruß, P. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)02028-2 · Cited by 361
Generation of Rx + /Pax6 + neural retinal precursors from embryonic stem cells
Ikeda, H. O., Osakada, F., Watanabe, K., Mizuseki, K., Haraguchi, T., Miyoshi, H., Kamiya, D., Honda, Y., Sasai, N., Yoshimura, N., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500010102 · Cited by 335
Self-citationAdult‐born hippocampal neurons mature into activity‐dependent responsiveness
Jessberger, S., & Kempermann, G. (2003) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2003.02986.x · Cited by 326
Chemokines Regulate the Migration of Neural Progenitors to Sites of Neuroinflammation
Belmadani, A. A., Tran, P. B., Ren, D., & Miller, R. J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0156-06.2006 · Cited by 322
Lee, S., Kim, H.-Y., Rogowska, J., Zhao, B., Bhide, P. G., Parent, J. M., & Lo, E. H. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4085-05.2006 · Cited by 292
Retinal cell fate determination and bHLH factors
Hatakeyama, J., & Kageyama, R. (2004) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2003.09.005 · Cited by 274
Belecky‐Adams, T. L., Tomarev, S. I., Li, H. S., Ploder, L., McInnes, R. R., Sundin, O. H., & Adler, R. (1997) · PubMed · Cited by 239
Wnt2b controls retinal cell differentiation at the ciliary marginal zone
Kubo, F., Takeichi, M., & Nakagawa, S. (2003) · Development · doi:10.1242/dev.00244 · Cited by 223
Fischer, A. J., McGuire, C. R., Dierks, B. D., & Reh, T. A. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-21-09387.2002 · Cited by 210
Liu, H. S., Mohamed, O. A., Dufort, D., & Wallace, V. A. (2003) · Developmental Dynamics · doi:10.1002/dvdy.10315 · Cited by 203
A Small‐Molecule Agonist of the Wnt Signaling Pathway
Liu, J., Wu, X., Mitchell, B., Kintner, C., Ding, S., & Schultz, P. G. (2005) · Angewandte Chemie International Edition · doi:10.1002/anie.200462552 · Cited by 142
Domingos, P. M. D. N., Itasaki, N., Jones, C. M., Mercurio, S., Sargent, M. G., Smith, J. C., & Krumlauf, R. K. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0431 · Cited by 115
Growth factors induce neurogenesis in the ciliary body
Fischer, A. J., & Reh, T. A. (2003) · Developmental Biology · doi:10.1016/s0012-1606(03)00178-7 · Cited by 111
Soluble factors and the development of rod photoreceptors
Levine, E. M., Fuhrmann, S., & Reh, T. A. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000686 · Cited by 109
How the Neural Retina Regenerates
Raymond, P. A., & Hitchcock, P. F. (2000) · Results and problems in cell differentiation · doi:10.1007/978-3-540-46826-4_11 · Cited by 83
Inoue, T., Kagawa, T., Fukushima, M., Shimizu, T., Yoshinaga, Y., Takada, S., Tanihara, H., & Taga, T. (2005) · Stem Cells · doi:10.1634/stemcells.2005-0124 · Cited by 81
Wnt/Frizzled Signaling during Vertebrate Retinal Development
Raay, T. J. V., & Vetter, M. L. (2004) · Developmental Neuroscience · doi:10.1159/000082277 · Cited by 80
Retinoic acid. A key molecule for eye and photoreceptor development.
Hyatt, G. A., & Dowling, J. E. (1997) · PubMed · Cited by 79
Kohno, H., Sakai, T., & Kitahara, K. (2005) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-005-0030-7 · Cited by 74
p53 regulates apoptotic retinal ganglion cell death induced by N-methyl-D-aspartate.
Li, Y., Schlamp, C. L., Poulsen, G. L., Jackson, M. W., Griep, A. E., & Nickells, R. W. (2002) · PubMed · Cited by 65
Retrovirus-mediated gene transfer to retinal explants
Hatakeyama, J., & Kageyama, R. (2002) · Methods · doi:10.1016/s1046-2023(02)00257-8 · Cited by 55
bHLH Genes and Retinal Cell Fate Specification
Yan, R., Ma, W., Liang, L., & Wang, S. (2005) · Molecular Neurobiology · doi:10.1385/mn:32:2:157 · Cited by 35
Cited by
Sorted by citations
Bringmann, A., Iandiev, I., Pannicke, T., Wurm, A., Hollborn, M., Wiedemann, P., Osborne, N. N., & Reichenbach, A. (2009) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.07.001 · Cited by 761
Müller glial cell reprogramming and retina regeneration
Goldman, D. J. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3723 · Cited by 652
Osakada, F., Ikeda, H. O., Mandai, M., Wataya, T., Watanabe, K., Yoshimura, N., Akaike, A., Sasai, Y., & Takahashi, M. (2008) · Nature Biotechnology · doi:10.1038/nbt1384 · Cited by 629
Self-citationEmerging roles of Wnts in the adult nervous system
Inestrosa, N. C., & Arenas, E. (2009) · Nature reviews. Neuroscience · doi:10.1038/nrn2755 · Cited by 622
The zebrafish as a model for complex tissue regeneration
Gemberling, M. P., Bailey, T. J., Hyde, D. R., & Poss, K. D. (2013) · Trends in Genetics · doi:10.1016/j.tig.2013.07.003 · Cited by 596
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
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 ›
Are you an author, or do you see a problem with this page? Request a review
