WNTs in synapse formation and neuronal circuitry

Abstract

Wnt proteins play important roles in wiring neural circuits. Wnts regulate many aspects of neural circuit generation through their receptors and distinct signalling pathways. In this review, we discuss recent findings on the functions of Wnts in various aspects of neural circuit formation, including neuronal polarity, axon guidance, synapse formation, and synaptic plasticity in vertebrate and invertebrate nervous systems.

Figure 1

Wnts regulate neuronal polarity. In C. elegans, ALM neuronal polarity is shaped by the Wnts CWN-1 and EGL-20 and the Ror receptor CAM-1, whereas PLM neuronal polarity is shaped by the Wnt LIN-44 and the Fz receptor LIN-17. Note that the Wnt (LIN-44, CWN-1, EGL-20) gradients high in posterior and low in anterior.

Figure 2

Wnts are involved in synaptogenesis by promoting synapse formation. (A) In the cerebellum, Wnt7a acts as a retrograde signal to regulate presynaptic assembly through Dvl- and Gsk3β-mediated signalling pathways. (B) In hippocampal neurons, Fz5 is required for Wnt7a-mediated synapse formation. The activation of Wnt7a increases presynaptic inputs, whereas the activation of Wnt5a decreases the number of presynaptic terminals.

Figure 3

Wnts are involved in synaptogenesis through inhibition of synapse formation. A local Wnt LIN-44 gradient negatively regulates DA9 synapse formation through its anti-synaptogenic activity.

Figure 4

Wnts play a role in activity-dependent synapse remodelling. Neuronal activity regulates Fz5 trafficking to and out of synapses, contributing to activity-mediated synapse remodelling. High-frequency stimulation (HFS) increases surface and synaptic localization of Fz5, whereas low-frequency stimulation (LFS) decreases surface and synaptic localization of Fz5.