Cell‐to‐Cell Signalling in Development: Wnt Signalling

Wnt signalling is an important cell-to-cell signalling mechanism, which is generally conserved among multicellular animals. Wnt signalling operates in the embryo and in adult stem cells, but also in human cancers. Frizzled receptors in the cell membrane are critical functional intermediaries between the extracellular Wnt signal and diverse signal transduction mechanisms that can be activated inside different responding cells. Coreceptors are involved in selecting more specific intracellular signal transduction mechanisms. Frizzled receptors and other Wnt signalling molecules are localised in cells to coordinate planar cell polarity in epithelial tissues and also to regulate morphogenetic movements in embryos. A well-studied intracellular Wnt signal transduction mechanism promotes stabilisation and nuclear localisation of the protein β-catenin to regulate transcription of specific target genes by interacting with deoxyribonucleic acid (DNA)-binding transcription factor proteins, such as the TCF/LEF proteins. Key Concepts: Wnt signalling functions in the embryo, to regulate stem cells and in disease such as cancer. Wnt signalling mechanisms regulate important cellular processes, such as cell fate specification, cell proliferation, cell differentiation, axon guidance and morphogenesis. Wnt proteins are lipid-modified secreted signals. Frizzled proteins function as cell membrane receptors for Wnt signals. Wnt/Frizzled signalling activates a network of diverse intracellular signal transduction pathways. One conserved branch of Wnt signal transduction causes stabilisation and nuclear localisation of the protein β-catenin. Nuclear β-catenin regulates transcription of specific target genes by interacting with DNA-binding proteins, such as TCF/LEF proteins. Other, β-catenin-independent Wnt signal transduction mechanisms also regulate the cytoskeleton and planar cell polarity. Feedback regulation and cross-regulation between different Wnt signal transduction branches is characteristic of Wnt signalling. Keywords: β-catenin; GSK3; Axin; APC; planar cell polarity; G-protein-coupled receptor; morphogenesis; cilia; cytoskeleton; TCF/LEF