Wnt Signaling Directs Neuronal Polarity and Axonal Growth

The establishment of neuronal polarity is driven by cytoskeletal remodeling that stabilizes and promotes the growth of a single axon from one of the multiple neurites. The importance of the local microtubule stabilization in this process has been revealed however, the external signals initiating the cytoskeletal rearrangements are not completely understood. In this study, we show that local activation of the canonical Wnt pathway regulates neuronal polarity and axonal outgrowth. We found that in the early stages of neuronal polarization, Wnt3a accumulates in one of the neurites of unpolarized cells and thereby could determine axon positioning. Subsequently, Wnt3a localizes to the growing axon, where it activates the canonical Wnt pathway and controls axon positioning and axonal length. We propose a model in which Wnt3a regulates the formation and growth of the axon by activating local intracellular signaling events leading to microtubule remodeling. [Display omitted] •Wnt3a distributes asymmetrically in early stages neurons•A spatially localized Wnt3a source determines axon positioning and early guidance•Concentration gradient of Wnt3a guides axonal outgrowth across a microfluidic chamber•Wnt3a directly controls microtubules remodeling Neuroscience; Molecular Neuroscience; Cellular Neuroscience