Spatial and temporal regulation of Wnt/beta-catenin signaling is essential for development of the retinal pigment epithelium.
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.
Fujimura
Naoko
N
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic.
Taketo
Makoto M
MM
Mori
Mikiro
M
Korinek
Vladimir
V
Kozmik
Zbynek
Z
D000818:Animals; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D004622:Embryo, Mammalian / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D019426:Integrases; D051379:Mice; D055213:Retinal Pigment Epithelium / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D051153:Wnt Proteins; D051176:beta Catenin; C045073:Cre recombinase; D019426:Integrases