Axonal growth:: where neurotrophins meet Wnts

Axonal guidance is influenced by many cues, including polypeptide trophic factors, cytokines, diffusible attractants and repellents and changes in calcium. How these signals are conveyed and integrated is not well defined. Recent data suggest that molecules of the canonical Writ signaling pathway may have direct actions on axonal growth through neurotrophin signaling. This surprising mechanism is supported by local inactivation of glycogen synthase kinase 3 beta (GSK-3 beta) by nerve growth factor through the integrin-linked kinase. Inhibition of GSK-3 beta provides a positive regulatory signal for the cytoskeleton re-arrangement involved in axon extension. Moreover, microtubule stabilization is stimulated by adenomatous polyposis coli protein, a downstream target of GSK3, in response to neurotrophins. Therefore, components of the Writ signaling pathway are downstream of trophic factors, providing new insights into cytoskeletal regulatory events during axonal growth.