Vangl-dependent planar cell polarity signalling is not required for neural crest migration in mammals.

Sophie E Pryor,Philipp Andre,Nicholas D E Greene,Dawn Savery,Yingzi Yang,Andrew J Copp,Valentina Massa

doi:10.1242/dev.111427

Abstract

The role of planar cell polarity (PCP) signalling in neural crest (NC) development is unclear. The PCP dependence of NC cell migration has been reported in Xenopus and zebrafish, but NC migration has not been studied in mammalian PCP mutants. Vangl2Lp/Lp mouse embryos lack PCP signalling and undergo almost complete failure of neural tube closure. Here we show, however, that NC specification, migration and derivative formation occur normally in Vangl2Lp/Lp embryos. The gene family member Vangl1 was not expressed in NC nor ectopically expressed in Vangl2Lp/Lp embryos, and doubly homozygous Vangl1/Vangl2 mutants exhibited normal NC migration. Acute downregulation of Vangl2 in the NC lineage did not prevent NC migration. In vitro, Vangl2Lp/Lp neural tube explants generated emigrating NC cells, as in wild type. Hence, PCP signalling is not essential for NC migration in mammals, in contrast to its essential role in neural tube closure. PCP mutations are thus unlikely to mediate NC-related birth defects in humans.

Highlights

The neural crest (NC) is a transient cell population that delaminates from the dorsal neural tube and migrates extensively, generating a variety of cell types (Kulesa et al, 2010; Sauka-Spengler and Bronner-Fraser, 2008)
NC specification and migration are normal in Vangl2Lp/Lp embryos The specification of NC cells was detected by whole-mount in situ hybridisation (WISH) for Sox9, a marker of premigratory NC (Cheung and Briscoe, 2003)
Migrating NC cells were detected by WISH for Erbb3, a neuregulin receptor tyrosine kinase (Garratt et al, 2000)

Summary

Introduction

The neural crest (NC) is a transient cell population that delaminates from the dorsal neural tube and migrates extensively, generating a variety of cell types (Kulesa et al, 2010; Sauka-Spengler and Bronner-Fraser, 2008). NC emigration is closely coordinated spatiotemporally with closure of the neural tube, and some genes [e.g. AP2α (Tfap2a), Cecr, Pax, Zic2] (Harris and Juriloff, 2007) are necessary for both embryonic events. Signalling via the planar cell polarity (PCP) pathway is required for neural tube closure in vertebrates, and recently PCP mutations were reported in human neural tube defects (Juriloff and Harris, 2012). The role of PCP signalling in NC migration, in mammals, remains unresolved. The vertebrate homologues of Drosophila ‘core’ PCP genes regulate many developmental processes, including convergent extension (CE) cell

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