Wnt signalling in development and disease

Abstract

Figure 1. A meeting on Wnt Signaling in Development and Disease took place between 12 and 15 September 2007, in the Max Delbrück Center for Molecular Medicine in Berlin‐Buch, Germany, and was organized by W. Birchmeier (Berlin, Germany) and T. Holstein (Heidelberg, Germany). Wnt signalling is implicated in numerous aspects of development, cell biology and physiology. This meeting brought together several leading scientists in the Wnt signalling field, who discussed their latest research in this rapidly growing discipline. The expanding number of diseases that are the consequence of mutations in components of the Wnt signalling pathway also attracted researchers with a more clinical interest. Many new insights were presented into the mechanics of Wnt signalling and the role of Wnts in development, regeneration, stem cells and cancer, which we have attempted to summarize in this meeting report. In the absence of Wnt ligands, β‐catenin is phosphorylated by a destruction complex that contains the scaffolding proteins axin and adenomatous polyposis coli (Apc), and the glycogen synthase kinase 3β (Gsk3β). Phosphorylated β‐catenin is recognized by the E3 ubiquitin ligase β‐TrCP and targeted for proteasomal degradation. Wnt signalling is initiated at the plasma membrane by the binding of Wnt ligands to the receptors Frizzled (Fz) and Arrow/LRP. The signal is then relayed in the cytoplasm through Dishevelled (Dsh/Dvl) and leads to inhibition of the destruction complex. Unphosphorylated β‐catenin can then localize to the nucleus where it binds to Tcf/Lef proteins and activates transcription through the recruitment of various cofactors (see Clevers (2006) and the Wnt homepage (http://www.stanford.edu/~rnusse/wntwindow.html) for reviews on Wnt signalling). The binding of Wnt to Fz/LRP leads to the phosphorylation of LRP6 by Gsk3β and casein kinase Iγ (CkIγ), which is necessary for correct Wnt signalling, presumably because axin can then dock to the phosphorylated residues. At the same time, Dvl is recruited …