Wnt-signaling in development and disease: News and surprises for the Wnt/b-catenin and Wnt/Planar Cell Polarity pathways

Marek Mlodzik

Wnt-signaling, via b-catenin or the planar cell polarity (PCP) branch, is crucial for development, organogenesis and tissue homeostasis and also cell polarity, and critically linked to many diseases. Wnt signaling is also critical in stem cell establishment and maintenance in (almost) all tissues. At the center of these pathways are the Wnt signals and their receptors, the Frizzled (Fz/Fzd) family of 7-pass trans-membrane proteins. While a lot is known about the architecture of the two main Wnt-pathways: the Wnt/b-catenin pathway and Wnt/PCP signaling, less is known about the regulation of signaling specificity and differences or similarities in pathway activation, and importantly how the “business-end” molecule in the Wnt/b-catenin pathway, b-catenin itself, is imported into the nucleus upon pathway activation. In this lecture, I will discuss new insights – with significant surprises – on Wnt-pathway specific regulation, new Wnt/PCP insights, and a novel mechanism required for nuclear translocation of b-catenin.