Reference - Detail
|Author||Vivancos V, Chen P, Spassky N, Qian D, Dabdoub A, Kelley M, Studer M, Guthrie S.|
|Title||Wnt activity guides facial branchiomotor neuron migration, and involves the PCP pathway and JNK and ROCK kinases.|
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 caudal high to rostral low 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.
|MeSH||Animals Cell Movement / genetics Cell Movement / physiology* Cell Polarity / genetics Cell Polarity / physiology* Embryo, Nonmammalian Female Frizzled Receptors / genetics Frizzled Receptors / metabolism* Gene Expression Regulation, Developmental Immunohistochemistry In Situ Hybridization JNK Mitogen-Activated Protein Kinases / genetics JNK Mitogen-Activated Protein Kinases / metabolism* Mice Motor Neurons / metabolism* Neural Pathways / metabolism Rhombencephalon / cytology Wnt Proteins / genetics Wnt Proteins / metabolism* Wnt-5a Protein rho-Associated Kinases / genetics rho-Associated Kinases / metabolism*|
|WOS Category||DEVELOPMENTAL BIOLOGY NEUROSCIENCES|
|Zebrafish||rw75 ((trilobite)(vangl2))? rw16 ((landlocked)(scribble1))? rw468 ((landlocked)(scribble1))? rw689 ((off-limit)(fz3a))?|