A β-Catenin-Dependent Wnt Pathway Mediates Anteroposterior Axon Guidance in C. elegans Motor Neurons

BACKGROUND: Wnts are secreted glycoproteins that regulate diverse aspects of development, including cell proliferation, cell fate specification and differentiation. More recently, Wnts have been shown to direct axon guidance in vertebrates, flies and worms. However, little is known about the intracellular signaling pathways downstream of Wnts in axon guidance. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the posterior C. elegans Wnt protein LIN-44 repels the axons of the adjacent D-type motor neurons by activating its receptor LIN-17/Frizzled on the neurons. Moreover, mutations in mig-5/Disheveled, gsk-3, pry-1/Axin, bar-1/β-catenin and pop-1/TCF, also cause disrupted D-type axon pathfinding. Reduced BAR-1/β-catenin activity in D-type axons leads to undergrowth of axons, while stabilization of BAR-1/β-catenin in a lin-23/SCF(β-TrCP) mutant results in an overextension phenotype. CONCLUSIONS/SIGNIFICANCE: Together, our data provide evidence that Wnt-mediated axon guidance can be transduced through a β-catenin-dependent pathway.