a β-catenin-dependent wnt pathway mediates anteroposterior axon guidance in c. elegans motor neurons一个β-catenin-dependent wnt通路调节前后的秀丽隐杆线虫运动神经元轴突的指导.pdfVIP

A b-Catenin-Dependent Wnt Pathway Mediates Anteroposterior Axon Guidance in C. elegans Motor Neurons ´ 1 2 1 Geraldine S. Maro *, Matthew P. Klassen , Kang Shen * 1 Howard Hughes Medical Institute, Department of Biology and Pathology, Stanford University, Stanford, California, United States of America, 2 Neurosciences Program, Stanford University, Stanford, California, United States of America Abstract 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/ b-catenin and pop-1/TCF, also cause disrupted D-type axon pathfinding. Reduced BAR- 1/b-catenin activity in D-type axons leads to undergrowth of axons, while stabilization of BAR-1/b-catenin in a lin-23/ SCFb-TrCP mutant results in an overextension phenotype. Conclusions/Significance: Together, our data provide evidence that Wnt-mediated axon guidance can be transduced through a b-catenin-dependent pathway. Citation: Maro GS, Klassen MP, Shen K (2009) A b-Catenin-Dependent Wnt Pathway Mediates Anteroposterior Axon Guidance in C. elegans Motor Neurons. PLoS ONE 4(3): e4690. doi:10.1371/journal.pone.0004690 ´ Editor: Alain Chedotal, Institut de la Vision, France Received November 15, 2008; Accepted January 29, 2009