title: Vangl-dependent planar cell polarity signalling is not required for neural crest migration in mammals.
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. Vangl2(Lp/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 Vangl2(Lp/Lp) embryos. The gene family member Vangl1 was not expressed in NC nor ectopically expressed in Vangl2(Lp/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, Vangl2(Lp/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.
authors.affiliation: Newlife Birth Defects Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Pryor
authors.affiliation: Newlife Birth Defects Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Massa
authors.affiliation: Newlife Birth Defects Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Dawn
authors.initials: D
authors.lastname: Savery
authors.affiliation: Genetic Disease Research Branch, National Human Genome Research Institute, 49 Convent Drive, MSC 4472, Bethesda, MD 20892, USA.
authors.forename: Philipp
authors.initials: P
authors.lastname: Andre
authors.affiliation: Genetic Disease Research Branch, National Human Genome Research Institute, 49 Convent Drive, MSC 4472, Bethesda, MD 20892, USA.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Newlife Birth Defects Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Nicholas D E
authors.initials: ND
authors.lastname: Greene
authors.affiliation: Newlife Birth Defects Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK a.copp@ucl.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Copp
mesh_terms: D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D016764:Cell Polarity / Q000502:physiology*; D006720:Homozygote; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D054259:Neural Tube / Q000196:embryology; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; C431577:Ltap protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C528120:Vangl1 protein, mouse
keywords: Cell migration; Embryo; Mouse; Neural crest; Neural tube; Planar cell polarity