Wnt activity guides facial branchiomotor neuron migration, and involves the PCP pathway and JNK and ROCK kinases

• Type of Material: Article
• Authors: Valerie Vivancos, King's College; Ping Helen Chen, Emory University; Nathalie Spassky, Hôpital de la Saltpetriere; Dong Qian, Emory University; Alain Dabdoub, University of California; Matthew Kelley, Porter Neuroscience Research Center; Michele Studer, Telethon Institute of Genetics and Medicine; Sarah Guthrie, King's College
• Language: English
• Date: 2009-02-11
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2009 Vivancos et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.neuraldevelopment.com/content/4/1/7
• Title of Journal or Parent Work: Neural Development
• ISSN: 1749-8104
• Volume: 4
• Issue: 7
• Grant/Funding Information: We thank the Wellcome Trust very much for funding the work described in this article.
• Research Categories: Biology, Neuroscience; Biology, Cell

Abstract

Background Wnt proteins play roles in many biological processes, including axon guidance and cell migration. In the mammalian hindbrain, facial branchiomotor (FBM) neurons undergo a striking rostral to caudal migration, yet little is known of the underlying molecular mechanisms. In this study, we investigated a possible role of Wnts and the planar cell polarity (PCP) pathway in this process. Results Here we demonstrate a novel role for Wnt proteins in guiding FBM neurons during their rostral to caudal migration in the hindbrain. We found that Wnt5a is expressed in a caudalhigh to rostrallow gradient in the hindbrain. Wnt-coated beads chemoattracted FBM neurons to ectopic positions in an explant migration assay. The rostrocaudal FBM migration was moderately perturbed in Wnt5a mutant embryos and severely disrupted in Frizzled3 mutant mouse embryos, and was aberrant following inhibition of Wnt function by secreted Frizzled-related proteins. We also show the involvement of the Wnt/PCP pathway in mammalian FBM neuron migration. Thus, mutations in two PCP genes, Vangl2 and Scribble, caused severe defects in FBM migration. Inhibition of JNK and ROCK kinases strongly and specifically reduced the FBM migration, as well as blocked the chemoattractant effects of ectopic Wnt proteins. Conclusion These results provide in vivo evidence that Wnts chemoattract mammalian FBM neurons and that Wnt5a is a candidate to mediate this process. Molecules of the PCP pathway and the JNK and ROCK kinases also play a role in the FBM migration and are likely mediators of Wnt signalling.