Scheme 2.

Schematic representation of Wnt/planar cell polarity (PCP) establishment, core components and signal transduction pathway. (a) Cell polarity is established in an epithelium based on the gradient of certain signalling molecules, such as Wnt5a ligands. It is mediated by two protein complexes that form on the opposite cell sites, and inter- and intracellular communication between these complexes provides the cells with a planar orientation axis pattern that can extend through the whole tissue. (b) The first complex is formed by a transmembrane frizzled receptor (Fzd) and cadherin EGF LAG seven-pass G-Type receptor (CELSR), which enable intercellular communication and cell–cell connection, and intracellular disheveled (DVL) and ankyrin repeat domain 6 (ANKRD6) proteins, which mediate intracellular signals. Similarly, the second complex is composed of transmembrane CELSR and Vangl planar cell polarity protein (VANGL) and the intracellular Prickle. The intracellular components are essential for negative feedback loops within each cell (they antagonise each other) and for activating signal transduction pathways. (c) Following Wnt ligand binding to Fzd receptor and ROR2 co-receptor, DVL is recruited to the membrane, which activates downstream signalling transductions. The activation signal is then transmitted to the adaptor protein dishevelled associated activator of morphogenesis (DAAM1-2) and small G proteins, such as Rac1, RhoA and Cdc42 as well as Rho-associated coiled kinase (ROCK1/2). The activation of GTPases triggers cytoskeleton rearrangements and activates transcriptions factors, such as c-jun NH2-terminal kinase (JNK) and activator protein1 (AP-1).