title: Convergent extension, planar-cell-polarity signalling and initiation of mouse neural tube closure.
abstract: Planar-cell-polarity (PCP) signalling is necessary for initiation of neural tube closure in higher vertebrates. In mice with PCP gene mutations, a broad embryonic midline prevents the onset of neurulation through wide spacing of the neural folds. In order to evaluate the role of convergent extension in this defect, we vitally labelled the midline of loop-tail (Lp) embryos mutant for the PCP gene Vangl2. Injection of DiI into the node, and electroporation of a GFP expression vector into the midline neural plate, revealed defective convergent extension in both axial mesoderm and neuroepithelium, before the onset of neurulation. Chimeras containing both wild-type and Lp-mutant cells exhibited mainly wild-type cells in the midline neural plate and notochordal plate, consistent with a cell-autonomous disturbance of convergent extension. Inhibitor studies in whole-embryo culture demonstrated a requirement for signalling via RhoA-Rho kinase, but not jun N-terminal kinase, in convergent extension and the onset of neural tube closure. These findings identify a cell-autonomous defect of convergent extension, requiring PCP signalling via RhoA-Rho kinase, during the development of severe neural tube defects in the mouse.
authors.affiliation: Neural Development Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ybot-Gonzalez
authors.forename: Dawn
authors.initials: D
authors.lastname: Savery
authors.forename: Dianne
authors.initials: D
authors.lastname: Gerrelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Signore
authors.forename: Claire E
authors.initials: CE
authors.lastname: Mitchell
authors.forename: Clare H
authors.initials: CH
authors.lastname: Faux
authors.forename: Nicholas D E
authors.initials: ND
authors.lastname: Greene
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Copp
mesh_terms: D000818:Animals; D019521:Body Patterning; D016764:Cell Polarity / Q000502:physiology*; D002490:Central Nervous System / Q000196:embryology / Q000254:growth & development*; D047108:Embryonic Development; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009436:Neural Tube Defects / Q000235:genetics*; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; D020742:rhoA GTP-Binding Protein