Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 175

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

β-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression

Open access
Westenskow, Peter, Piccolo, Stefano, Fuhrmann, Sabine·2009·Development
DOI 10.1242/dev.032136
Open this paper in CoChat — free account

Abstract

The retinal pigment epithelium (RPE) consists of a monolayer of cuboidal,pigmented cells that is located between the retina and the choroid. The RPE is vital for growth and function of the vertebrate eye and improper development results in congenital defects, such as microphthalmia or anophthalmia, or a change of cell fate into neural retina called transdifferentiation. The transcription factors microphthalmia-associated transcription factor (Mitf)and orthodenticle homolog 2 (Otx2) are crucial for RPE development and function; however, very little is known about their regulation. Here, by using a Wnt-responsive reporter, we show that the Wnt/β-catenin pathway is activated in the differentiating mouse RPE. Cre-mediated, RPE-specific disruption of β-catenin after the onset of RPE specification causes severe defects, resulting in microphthalmia with coloboma, disturbed lamination, and mislocalization of adherens junction proteins. Uponβ-catenin deletion, the RPE transforms into a multilayered tissue in which the expression of Mitf and Otx2 is downregulated, while retina-specific gene expression is induced, which results in the transdifferentiation of RPE into retina. Chromatin immunoprecipitation (ChIP) and luciferase assays indicate that β-catenin binds near to and activates potential TCF/LEF sites in the Mitf and Otx2 enhancers. We conclude that Wnt/β-catenin signaling is required for differentiation of the RPE by directly regulating the expression of Mitf and Otx2. Our study is the first to show that an extracellular signaling pathway directly regulates the expression of RPE-specific genes such as Mitf and Otx2, and elucidates a new role for the Wnt/β-catenin pathway in organ formation and development.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1242/dev.032136

Cites

1 of 1 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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

Show all 1 references

Research works printed but not linked: 40

  1. Bharti, K., Nguyen, M. T., Skuntz, S., Bertuzzi, S. and Arnheiter, H. (2006). The other pigment cell: specification and development of the pigmented epithelium of the vertebrate eye. Pigment Cell Re.s19,380-394. · DOI · Paper page
  2. Bharti, K., Liu, W., Csermely, T., Bertuzzi, S. and Arnheiter,H. (2008). Alternative promoter use in eye development: the complex role and regulation of the transcription factor MITF. Development135,1169-1178. · DOI
  3. Burmeister, M., Novak, J., Liang, M. Y., Basu, S., Ploder, L.,Hawes, N. L., Vidgen, D., Hoover, F., Goldman, D., Kalnins, V. I. et al.(1996). Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation. Nat. Genet.12,376-384. · DOI · Paper page
  4. Burns, C. J., Zhang, J., Brown, E. C., Van Bibber, A. M., Van Es, J., Clevers, H., Ishikawa, T. O., Taketo, M. M., Vetter, M. L. and Fuhrmann, S. (2008). Investigation of Frizzled-5 during embryonic neural development in mouse. Dev. Dyn.237,1614-1626. · DOI
  5. Clark, A. M., Yun, S., Veien, E. S., Wu, Y. Y., Chow, R. L.,Dorsky, R. I. and Levine, E. M. (2008). Negative regulation of Vsx1 by its paralog Chx10/Vsx2 is conserved in the vertebrate retina. Brain Res.1192,99-113. · doi:10.1016/j.brainres.2007.06.007
  6. Fu, X., Sun, H., Klein, W. H. and Mu, X.(2006). beta-catenin is essential for lamination but not neurogenesis in mouse retinal development. Dev. Biol.299,424-437. · doi:10.1016/j.ydbio.2006.08.015
  7. Fuhrmann, S., Levine, E. M. and Reh, T. A.(2000). Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick. Development127,4599-4609. · DOI · Paper page
  8. Fuhrmann, S., Riesenberg, A. N., Mathiesen, A. M., Brown, E. C.,Vetter, M. L. and Brown, N. L. (2009). Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina. Invest. Ophthalmol. Vis. Sci.50,432-440. · doi:10.1167/iovs.08-2270
  9. Gage, P. J., Suh, H. and Camper, S. A. (1999). Dosage requirement of Pitx2 for development of multiple organs. Development126,4643-4651. · DOI · Paper page
  10. Galceran, J., Farinas, I., Depew, M. J., Clevers, H. and Grosschedl, R. (1999). Wnt3a-/-like phenotype and limb deficiency in Lef1-/-Tcf1-/- mice. Genes Dev.13,709-717. · DOI · Paper page
  11. Galceran, J., Miyashita-Lin, E. M., Devaney, E., Rubenstein, J. L. and Grosschedl, R. (2000). Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1. Development127,469-482. · DOI · Paper page
  12. Hallikas, O., Palin, K., Sinjushina, N., Rautiainen, R.,Partanen, J., Ukkonen, E. and Taipale, J. (2006). Genome-wide prediction of mammalian enhancers based on analysis of transcription-factor binding affinity. Cell124, 47-59. · DOI · Paper page
  13. Hsu, S. C., Galceran, J. and Grosschedl, R.(1998). Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with beta-catenin. Mol. Cell. Biol.18,4807-4818. · DOI · Paper page
  14. Huh, S., Hatini, V., Marcus, R. C., Li, S. C. and Lai, E.(1999). Dorsal-ventral patterning defects in the eye of BF-1-deficient mice associated with a restricted loss of shh expression. Dev. Biol.211,53-63. · DOI
  15. Jho, E. H., Zhang, T., Domon, C., Joo, C. K., Freund, J. N. and Costantini, F. (2002). Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol. Cell. Biol.22,1172-1183. · DOI · Paper page
  16. Labbe, E., Letamendia, A. and Attisano, L.(2000). Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways. Proc. Natl. Acad. Sci. USA97,8358-8363. · DOI · Paper page
  17. Liu, H., Mohamed, O., Dufort, D. and Wallace, V. A.(2003). Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retina. Dev. Dyn.227,323-334. · DOI · Paper page
  18. Liu, H., Thurig, S., Mohamed, O., Dufort, D. and Wallace, V. A. (2006). Mapping canonical Wnt signaling in the developing and adult retina. Invest. Ophthalmol. Vis. Sci.47,5088-5097. · DOI
  19. Maretto, S., Cordenonsi, M., Dupont, S., Braghetta, P.,Broccoli, V., Hassan, A. B., Volpin, D., Bressan, G. M. and Piccolo, S.(2003). Mapping Wnt/beta-catenin signaling during mouse development and in colorectal tumors. Proc. Natl. Acad. Sci. USA100,3299-3304. · DOI · Paper page
  20. Martinez-Morales, J. R., Signore, M., Acampora, D., Simeone, A. and Bovolenta, P. (2001). Otx genes are required for tissue specification in the developing eye. Development128,2019-2030. · DOI · Paper page
  21. Martinez-Morales, J. R., Dolez, V., Rodrigo, I., Zaccarini, R.,Leconte, L., Bovolenta, P. and Saule, S. (2003). OTX2 activates the molecular network underlying retina pigment epithelium differentiation. J. Biol. Chem.278,21721-21731. · DOI · Paper page
  22. Martinez-Morales, J. R., Rodrigo, I. and Bovolenta, P.(2004). Eye development: a view from the retina pigmented epithelium. BioEssays26,766-777. · DOI · Paper page
  23. Molenaar, M., van de Wetering, M., Oosterwegel, M.,Peterson-Maduro, J., Godsave, S., Korinek, V., Roose, J., Destree, O. and Clevers, H. (1996). XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell86,391-399. · DOI · Paper page
  24. Muller, F., Rohrer, H. and Vogel-Hopker, A.(2007). Bone morphogenetic proteins specify the retinal pigment epithelium in the chick embryo. Development134,3483-3493. · DOI
  25. Nguyen, M. and Arnheiter, H. (2000). Signaling and transcriptional regulation in early mammalian eye development: a link between FGF and MITF. Development127,3581-3591. · DOI · Paper page
  26. Perron, M., Boy, S., Amato, M. A., Viczian, A., Koebernick, K.,Pieler, T. and Harris, W. A. (2003). A novel function for Hedgehog signalling in retinal pigment epithelium differentiation. Development130,1565-1577. · DOI · Paper page
  27. Raymond, S. M. and Jackson, I. J. (1995). The retinal pigmented epithelium is required for development and maintenance of the mouse neural retina. Curr. Biol.5,1286-1295. · DOI · Paper page
  28. Rizzolo, L. J. (2007). Development and role of tight junctions in the retinal pigment epithelium. Int. Rev. Cytol.258,195-234. · DOI · Paper page
  29. Sakami, S., Etter, P. and Reh, T. A. (2008). Activin signaling limits the competence for retinal regeneration from the pigmented epithelium. Mech. Dev.125,106-116. · DOI
  30. Schmidt, C. and Patel, K. (2005). Wnts and the neural crest. Anat. Embryol.209,349-355. · DOI
  31. Scholtz, C. L. and Chan, K. K. (1987). Complicated colobomatous microphthalmia in the microphthalmic (mi/mi) mouse. Development99,501-508. · DOI
  32. Soriano, P. (1999). Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet.21, 70-71. · DOI · Paper page
  33. Strauss, O. (2005). The retinal pigment epithelium in visual function. Physiol. Rev.85,845-881. · DOI · Paper page
  34. Stroeva, O. G. (1960). Experimental analysis of the eye morphogenesis in mammals. J. Embryol.8, 349-368. · doi:10.1242/dev.8.3.349
  35. van Genderen, C., Okamura, R. M., Farinas, I., Quo, R. G.,Parslow, T. G., Bruhn, L. and Grosschedl, R. (1994). Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev.8,2691-2703. · DOI · Paper page
  36. Verbeek, S., Izon, D., Hofhuis, F., Robanus-Maandag, E., te Riele, H., van de Wetering, M., Oosterwegel, M., Wilson, A., MacDonald, H. R. and Clevers, H. (1995). An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature374, 70-74. · DOI · Paper page
  37. West-Mays, J. A., Zhang, J., Nottoli, T., Hagopian-Donaldson,S., Libby, D., Strissel, K. J. and Williams, T. (1999). AP-2alpha transcription factor is required for early morphogenesis of the lens vesicle. Dev. Biol.206,46-62. · DOI · Paper page
  38. Yost, C., Torres, M., Miller, J. R., Huang, E., Kimelman, D. and Moon, R. T. (1996). The axis-inducing activity, stability,and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. Genes Dev.10,1443-1454. · DOI · Paper page
  39. Zhang, X.-M. and Yang, X.-J. (2001). Temporal and spatial effects of Sonic Hedgehog signaling in chick eye morphogenesis. Dev. Biol.233,271. · DOI · Paper page
  40. Zhao, S., Thornquist, S. C. and Barnstable, C. J.(1995). In vitro transdifferentiation of embryonic rat retinal pigment epithelium to neural retina. Brain. Res.677,300-310. · DOI

Cited by

See all 175

Metadata

Authors
Westenskow, P., Piccolo, S., & Fuhrmann, S.
Venue
Development
Publisher
The Company of Biologists
Published
2009-08-01
Volume
136
Issue
15
Pages
2505-2510
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.032136
OpenAlex
W2053928527
Cited by
175
References
1
FWCI
4.44
Type
journal article
Language
en
Open access
green

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

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: β-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression. https://app.cochat.ai/papers/10.1242/dev.032136
The paper
Westenskow, P., Piccolo, S., & Fuhrmann, S. (2009). β-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression. Development. https://doi.org/10.1242/dev.032136

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.