Figure 3.

A schematic representation of the canonical Wnt signaling pathway. Norrin and Wnt act as ligands to bind FZD4 that interact with LRP5. In the absence of Wnt signaling, beta-catenin is phosphorylated and subjected to proteosomal degradation. In the presence of Wnt signaling, beta-catenin accumulates in the cytoplasm and enters the nucleus. Its subsequent interactions with a member of Tcf/Lef family activate the transcription of Wnt target genes. It was also shown that TSPAN12 is a component of the norrin-LRP5-FZD4 signaling complex and enhances the levels of norrin-beta-catenin signaling but not Wnt-beta-catenin signaling. Because of mutations in NDP, FZD4, LRP5 and TSPAN12 genes, abnormal signaling may occur which may result in defective Wnt target genes activation that may give rise to FEVR and ROP pathology. AD = autosomal dominant; AR = autosomal recessive; XL = X-linked recessive; FEVR = familial exudative vitreoretinopathy; ROP = retinopathy of prematurity; NDP = Norrie disease pseudoglioma.