Wnt factors in axonal remodelling and synaptogenesis

Abstract

Wiring' of the central nervous system is accomplished by the precise and co-ordinated behaviour of neuronal cells. Proper navigation of axons and formation of synaptic contacts with the correct targets are essential. Although several signalling molecules that control axon guidance, target selection and formation of synapses have been identified, little is known about how these proteins lead to changes in the axonal cytoskeleton. Wnt signalling factors have been shown to induce axonal remodelling in developing neurons. As several components of the Wnt signalling pathway are known, studies on Wnt factors could elucidate the mechanisms by which extracellular molecules regulate the neuronal cytoskeleton. Wnt-7a induces axonal spreading and subsequent increases in synaptic protein levels in mouse cerebellar neurons. These findings suggest a role for Wnt-7a in axon guidance and synapse formation in the developing cerebellum. Based on analyses of the axonal cytoskeleton, a model is proposed in which Wnt-7a induces axonal remodelling by inhibiting glycogen synthase kinase-3 beta (GSK-3 beta), a serine/threonine kinase. Inhibition of GSK-3 beta leads to a decrease in a phosphorylated form of microtubule-associated protein-1B (MAP-1B), a protein involved in microtubule assembly, and a concomitant decrease in the level of stable microtubules. This chapter discusses the novel role of Wnt factors in regulating the axonal cytoskeleton during neuronal development.