Spatial and temporal regulation of Wnt/beta-catenin signaling is essential for development of the retinal pigment epithelium
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19596317
DOI
10.1016/j.ydbio.2009.07.002
PII: S0012-1606(09)01035-5
Knihovny.cz E-resources
- MeSH
- beta Catenin metabolism MeSH
- Cell Differentiation MeSH
- Chromatin Immunoprecipitation MeSH
- Embryo, Mammalian metabolism MeSH
- Gene Expression MeSH
- Immunohistochemistry MeSH
- Integrases MeSH
- Mice MeSH
- Wnt Proteins metabolism MeSH
- Retinal Pigment Epithelium growth & development metabolism MeSH
- Signal Transduction * MeSH
- Transfection MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- beta Catenin MeSH
- Cre recombinase MeSH Browser
- Integrases MeSH
- Wnt Proteins MeSH
Wnt/beta-catenin signaling is highly active in the dorsal retinal pigment epithelium (RPE) during eye development. To study the role of Wnt/beta-catenin signaling in the RPE development we used a conditional Cre/loxP system in mice to inactivate or ectopically activate Wnt/beta-catenin signaling in the RPE. Inactivation of Wnt/beta-catenin signaling results in transdifferentiation of RPE to neural retina (NR) as documented by downregulation of RPE-specific markers Mitf and Otx2 and ectopic expression of NR-specific markers Chx10 and Rx, respectively. In contrast, ectopic activation of Wnt/beta-catenin signaling results in the disruption of the RPE patterning, indicating that precise spatial and temporal regulation of Wnt/beta-catenin signaling is required for normal RPE development. Using chromatin immunoprecipitation (ChIP) and reporter gene assays we provide evidence that Otx2 and RPE-specific isoform of Mitf, Mitf-H, are direct transcriptional targets of Wnt/beta-catenin signaling. Combined, our data suggest that Wnt/beta-catenin signaling plays an essential role in development of RPE by maintaining or inducing expression of Mitf and Otx2.
References provided by Crossref.org
WNT/β-Catenin Signaling in Vertebrate Eye Development
Genetic interaction between Pax6 and β-catenin in the developing retinal pigment epithelium
