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

被引:482
作者
Curtin, JA
Quint, E
Tsipouri, V
Arkell, RM
Cattanach, B
Copp, AJ
Henderson, DJ
Spurr, N
Stanier, P
Fisher, EM
Nolan, PM
Steel, KP
Brown, SDM
Gray, IC
Murdoch, JN [1 ]
机构
[1] MRC, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England
[2] GlaxoSmithKline Pharmaceut, Harlow CM19 5AD, Essex, England
[3] MRC, Inst Hearing Res, Nottingham NG7 2RD, England
[4] Univ London, Inst Child Hlth, Neural Dev Unit, London WC1N 1EH, England
[5] Univ Newcastle Upon Tyne, Inst Human Genet, Int Ctr Life, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England
[6] Univ London Imperial Coll Sci Technol & Med, Sch Med, Dept Obstet & Gynaecol, Inst Reprod & Dev Biol, London W12 0NN, England
[7] Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1016/S0960-9822(03)00374-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Celar1, 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.
引用
收藏
页码:1129 / 1133
页数:5
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