Identification of Wnt/β-catenin Modulated Genes in the Developing Retina

Mol Vis. 2012;18:645-56. Epub 2012 Mar 16.

Abstract

Purpose: During mammalian eye development, the restriction of Wnt/β-catenin signaling at the junction of the neural retina and the retinal pigment epithelium in the peripheral eyecup is required for the development of the ciliary margin, a non-neural region of the eyecup that is the precursor of the ciliary body and iris of the adult eye.

Methods: To identify genes that are modulated by β-catenin activity in the embryonic retina, we performed gene expression profiling in Li(+)-treated retinal explants, a pharmacological model of β-catenin activation. The Li(+)-modulated gene data set was searched for β-catenin/T-cell specific transcription factor binding sites.

Results: Functional annotations of this data set revealed significant enrichments for genes involved in chromatin organization, neurogenesis, and cell motion/migration. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis confirmed the modulation of 12 genes in Li(+)-treated explants and retinas of mice with Cre-mediated induction of constitutively active β-catenin (β-cat(act)). In situ hybridization revealed β-catenin-specific upregulation of cyclin-dependent kinase inhibitor 1A (P21) [Cdkn1a] and tumor necrosis factor receptor superfamily, member 19 (Tnfrsf19) in the developing retina consistent with the antineurogenic and proliferation changes associated with ectopic Wnt/β-catenin signaling in the eyecup.

Conclusions: This data set of Li(+)-modulated genes provides a valuable resource for characterizing the Wnt/ β-catenin regulated gene network in eyecup patterning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo, Mammalian
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / drug effects*
  • Lithium Chloride / pharmacology
  • Mice
  • Mice, Transgenic
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / metabolism*
  • Tissue Culture Techniques
  • Up-Regulation
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / genetics
  • beta Catenin / metabolism*
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*

Substances

  • Receptors, Tumor Necrosis Factor
  • Tnfrsf19 protein, mouse
  • Wnt Proteins
  • beta Catenin
  • Pak1 protein, mouse
  • p21-Activated Kinases
  • Lithium Chloride