Eyeing Up New Wnt Pathway Players

摘要

It is somewhat perplexing that an apparently limitless diversity of biological events can be controlled by reiterative use of the same, relatively simple signaling pathway. This may partly be due to the fact that many of the key Wnt pathway components occur more than once in animal genomes, such that multiple parallel versions of the pathway can operate in the same animal. The mammalian genome encodes two to four versions of many pathway components;however most diversity occurs at the ligand-receptor level. For example,mammals have around 20 Wnt ligands and 10 Frizzled receptors, which in different combinations regulate a variety of different processes including cell fate decisions during development and tissue repair in the adult. In this issue of Cell, Ye et al. (2009) and Junge et al. (2009) report on a group of hereditary retinopathies, including Norrie disease, that are associated with mutations in Wnt ligands and their Frizzled receptors. These two studies investigate how the ligand Norrin (which is not related to Wnt ligand) activates the canonical Wnt signaling pathway via the Frizzled-4 receptor leading to activation of β-catenin and vascularization of the developing retina. They also identify a new player in the Norrin/β-catenin signaling pathway and shed light on the diversification of the Wnt signaling pathway at the ligand-receptor level.