First Author | Fujimura N | Year | 2009 |
Journal | Dev Biol | Volume | 334 |
Issue | 1 | Pages | 31-45 |
PubMed ID | 19596317 | Mgi Jnum | J:153566 |
Mgi Id | MGI:4365713 | Doi | 10.1016/j.ydbio.2009.07.002 |
Citation | Fujimura N, et al. (2009) Spatial and temporal regulation of Wnt/beta-catenin signaling is essential for development of the retinal pigment epithelium. Dev Biol 334(1):31-45 |
abstractText | 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. |