Wnt signaling and neurite outgrowth: insights and questions

Wnt signaling consists of a highly conserved set of biochemical pathways that have a multitude of functions during embryonic development and in the adult. The Wnt proteins are extracellular agents that often act as gradient morphogens, indicating that their distribution in tissues is tightly controlled. This attribute is also characteristic of factors that regulate neurite outgrowth and guide axons precisely to their specific destinations. Several studies in various species now have established that Wnts and their receptors have an important role in axonal guidance. Different ligand/receptor combinations have been identified that mediate this activity in many of the experimental models. Clues about downstream effector molecules have come from in vitro systems. In this article, the authors review the results from many of these models, evaluate what is known about the associated signaling pathways and speculate about the direction of future research.