Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse

John A. Curtin, Elizabeth Quint, Vicky Tsipouri, Ruth M. Arkell, Bruce Cattanach, Andrew J. Copp, Deborah J. Henderson, Nigel Spurr, Philip Stanier, Elizabeth M. Fisher, Patrick M. Nolan, Karen P. Steel, Steve D.M. Brown, Ian C. Gray, Jennifer N. Murdoch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

515 Citations (Scopus)

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 [2, 3]. 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.

Original languageEnglish
Pages (from-to)1129-1133
Number of pages5
JournalCurrent Biology
Volume13
Issue number13
DOIs
Publication statusPublished - 1 Jul 2003
Externally publishedYes

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