Wnt7b Modulates Axon Differentiation and Extension via JNK-Mediated Cytoskeleton Dynamics

Abstract Neuronal polarization and axon growth are critical processes for neuronal cell differentiation and maturation. Wingless-type family proteins (Wnts) have been implied as key regulators of neuronal development; however, little is known about the cellular mechanisms by which they regulate axon growth. In this study, we investigated the role of Wnt7b on axon differentiation and elongation in hippocampal neurons and we also tried to describe the underlying mechanism involved in that process. Results indicated that Wnt7b accelerates the polarization of neurons and promotes axon elongation since most undifferentiated neurons polarized in the presence of Wnt7b and later on, elicited longer axons compared to controls. To go further, we found that this process was mediated by JNK pathway since its inhibition by a pharmacological agent or expressing a dominant negative construct blocked the Wnt7b effect on axonal elongation. Moreover, Wnt7b induced a locally activation of JNK at the axonal growth and changes in the cytoskeleton. In this sense, Wnt stimulation promoted microtubule stabilization along the newly-formed axons and protrusion of dynamic microtubules at the growth cones that likely facilitate axon extension. Together, our findings define Wnt7b as a crucial factor in the modulation of axon differentiation and extension by activating JNK pathway.