Wntbeta-catenin Signaling in Development of the Ciliary Margin in the Murine Eye

Abstract

The ciliary body (CB) of the vertebrate eye is located in the peripheral region of the retina and is involved in lens accommodation and production of aqueous humor. The CB develops from the ciliary margin (CM) where non-neural epithelial tissue differentiates from the neural ectoderm during embryonic development. The CM/CB represents an interesting area of study since the pigmented layer of the CM is reported to accommodate a pool of adult retinal stem cells. In fish and amphibians, these stem cells facilitate retinal growth and replenishment although this has yet to be observed in the mammalian retina. Previous studies have reported that the canonical Wnt signaling pathway has a role in development of the CM. Activation of this pathway both in vitro and in vivo resulted in an increase of CM markers at the expense of neural retinal markers and also resulted in an inhibition of neurogenesis in the retina. In this study, I show a preliminary screen of genes that playa role in Wnt mediated development of the CM. Using microarray analysis, quantitative real-time PCR, and in situ hybridization, I have identified candidate Wnt target genes in addition to known effectors of Wnt signaling in CM development. Additionally, I have begun a preliminary investigation to elucidate the role of the CM marker, Msx1, as a potential Wnt effector in CM development by showing that expression of this gene results in the downregulation of several bHLH transcription factors that are required for retinal neurogenesis. These findings provide some insights in how CM development is regulated by effectors of Wnt signaling.