title: Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse.
abstract: We identified two novel mouse mutants with abnormal head-shaking behavior and neural tube defects during the course of independent ENU mutagenesis experiments. The heterozygous and homozygous mutants exhibit defects in the orientation of sensory hair cells in the organ of Corti, indicating a defect in planar cell polarity. The homozygous mutants exhibit severe neural tube defects as a result of failure to initiate neural tube closure. We show that these mutants, spin cycle and crash, carry independent missense mutations within the coding region of Celsr1, encoding a large protocadherin molecule [1]. Celsr1 is one of three mammalian homologs of Drosophila flamingo/starry night, which is essential for the planar cell polarity pathway in Drosophila together with frizzled, dishevelled, prickle, strabismus/van gogh, and rhoA. The identification of mouse mutants of Celsr1 provides the first evidence for the function of the Celsr family in planar cell polarity in mammals and further supports the involvement of a planar cell polarity pathway in vertebrate neurulation.
authors.affiliation: GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, CM19 5AW, United Kingdom.
authors.forename: John A
authors.initials: JA
authors.lastname: Curtin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Quint
authors.forename: Vicky
authors.initials: V
authors.lastname: Tsipouri
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Arkell
authors.forename: Bruce
authors.initials: B
authors.lastname: Cattanach
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Copp
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Henderson
authors.forename: Nigel
authors.initials: N
authors.lastname: Spurr
authors.forename: Philip
authors.initials: P
authors.lastname: Stanier
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Fisher
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Nolan
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
authors.forename: Ian C
authors.initials: IC
authors.lastname: Gray
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Murdoch
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D002874:Chromosome Mapping; D006199:Hair Cells, Auditory, Inner / Q000503:physiopathology* / Q000648:ultrastructure; D017403:In Situ Hybridization; D051379:Mice; D008855:Microscopy, Electron, Scanning; D020125:Mutation, Missense / Q000235:genetics*; D009436:Neural Tube Defects / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology
chemical_list: C117380:Celsr1 protein, mouse; D043562:Receptors, G-Protein-Coupled