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

Valȳrie Vivancos,Alain Dabdoub,Dong Qian,Ping Chen,Nathalie Spassky,Michȳle Studer,Matthew Kelley,Sarah Guthrie

doi:10.1186/1749-8104-4-7

Abstract

BackgroundWnt 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.ResultsHere 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.ConclusionThese 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.

Highlights

Neuronal migration is a fundamental feature of the developing nervous system [1]
In this paper we demonstrate that the Wnt/planar cell polarity (PCP) pathway functions in mammalian facial branchiomotor (FBM) migration via an attractant mechanism
An in vivo role for Wnts is suggested by the finding that attenuation of endogenous Wnt signalling using secreted frizzed-related protein (SFRP), or by genetic loss of function of Wnt5a, disrupts the FBM migration

Summary

Introduction

A striking migration is undertaken by the facial branchiomotor neurons (FBMs) of the mammalian embryonic hindbrain. FBM neurons differentiate within rhombomere 4 (r4), while facial visceral motor neurons differentiate in r5 [2,3]. There is very little information about the molecules that drive FBM migration in the mouse embryo. We demonstrate for the first time a role for the Wnt/planar cell polarity (PCP) pathway in this process in mammals. Wnt proteins play roles in many biological processes, including axon guidance and cell migration. Facial branchiomotor (FBM) neurons undergo a striking rostral to caudal migration, yet little is known of the underlying molecular mechanisms. We investigated a possible role of Wnts and the planar cell polarity (PCP) pathway in this process

Methods

Results

Discussion

Conclusion