FIGURE 1.

The main branches ofWnt signalling pathways in neuronal development. Wnt factors bind to their classical receptor Frizzleds (Fz) or interact with tyrosine kinase receptors such as RYK, ROR2, and also IGF1R depending on the cellular context. In the canonical or WNT/β-catenin pathway Wnt also interacts with the LRP5/6 co-receptor and activates Dvl that contains three domains involving in different neuronal functions. Activation of Dvl mainly results in the GSK3β inhibition and the β-catenin accumulation in the cytosol which translocates to the nucleus where it activates specific gene transcription. Divergent pathways have been shown to control axon and dendrite morphology and presynaptic function. In the planar cell polarity (PCP) pathway Wnt binds to Fz and activates Dvl, which in turns signals to small Rho-GTPases proteins. Activation of Rac induces changes in the activity of JNK leading to changes in the cytoskeleton. This cascade was implied in dendrite development and complexity. In the Wnt/calcium pathway, activation of Dvl induces the increase of intracellular level of calcium and activation of PKC and CamKII affecting the transcription of NF-AT nuclear factor. However, divergent cascades involving the activation of CamKII have been identified to modulate neuronal polarity, dendritic spines morphology and synapses.