Spatial and Temporal Regulation of Wnt/beta-catenin Signaling Is Essential for Development of the Retinal Pigment Epithelium

Dev Biol. 2009 Oct 1;334(1):31-45. doi: 10.1016/j.ydbio.2009.07.002. Epub 2009 Jul 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Chromatin Immunoprecipitation
  • Embryo, Mammalian / metabolism
  • Gene Expression
  • Immunohistochemistry
  • Integrases
  • Mice
  • Retinal Pigment Epithelium / growth & development*
  • Retinal Pigment Epithelium / metabolism
  • Signal Transduction*
  • Transfection
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • Wnt Proteins
  • beta Catenin
  • Cre recombinase
  • Integrases