Figure 1.

Schematic illustration of Wnt/β‐catenin signalosome assembly. (A) Emerging model of Wnt ‘off’ state in which FZD receptor dimers and inactive LRP5/6 dimers form inactive complexes, which bind monomeric Dishevelled (Dvl). (B) Emerging model of Wnt ‘on’ state in which Wnts drive FZD oligomerization by stabilizing FZD CRD interactions, inducing conformational changes in LRP5/6 dimers and thus increasing local concentrations of Dishevelled, which ultimately permits efficient Dishevelled/Axin co‐polymerization. These events are responsible for intracellular Wnt signalosome assembly and sequestration of the β‐catenin destruction complex. Normal levels of Wnt signalling determine proper vertebrate development and stem cell programming, among many other functions, while excessively high or low levels of signalling have pathogenic outcomes.