Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retina

Abstract

The neuroepithelial layer of the developing eyecup contains multipotential precursor cells that give rise to all of the neurons and the one glial cell type present in the adult retina. Patterning within the retinal neuroepithelium is regulated by cell intrinsic as well as cell extrinsic mechanisms. Although the identity of some of the signaling molecules that regulate retinal development is known, the function of many others, especially members of the Wnt family, has yet to be characterized in the context of retinal development. We undertook a comprehensive in situ hybridization analysis to examine the expression of Wnt pathway components in the developing and adult mouse neural retina. Our findings confirm and extend previous expression studies in mice and other vertebrates, as we show that Wnt-3, -5a, -5b, and -7b are expressed in the neural retina and that there is a dynamic pattern of Wnt receptor (Mouse frizzled [Mfz]) and Wnt antagonist (Secreted-frizzled-related protein [Sfrp]) gene expression in the embryonic and perinatal neural retina. Moreover, we show that Wnt-13 is expressed in the pigment epithelium overlying the distal part of the eyecup and the ciliary margin and that Mfz-4, -6, and -7 are expressed in different regions within the ciliary margin. To determine where activation of canonical Wnt signaling is occurring in the retina, we examined reporter gene expression in TCF/Lef-LacZ mice and we demonstrate that the highest levels of beta-gal activity are found in the ciliary margin, adjacent to and within the Wnt-13 expression domain, implicating Wnt-13 signaling in the development of the ciliary margin and its derivatives.