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; Elizabeth Orton

doi:10.1016/S0960-9822(03)00374-9

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, Elizabeth Orton

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	1129-1133
Number of pages	4
Journal	Current Biology
Volume	13
Issue number	13
DOIs	https://doi.org/10.1016/S0960-9822(03)00374-9
Publication status	Published - 1 Jul 2003

Keywords

Animals
genetics: Cell Polarity
Chromosome Mapping
Comparative Study
physiopathology: Hair Cells, Inner
In Situ Hybridization
Mice
Microscopy, Electron, Scanning
genetics: Mutation, Missense
physiopathology: Neural Tube Defects
genetics: Receptors, G-Protein-Coupled
Research Support, Non-U.S. Gov't
Sequence Analysis, DNA
physiology: Signal Transduction

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10.1016/S0960-9822(03)00374-9

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Curtin, J. A., Quint, E., Tsipouri, V., Arkell, R. M., Cattanach, B., Copp, A. J., Henderson, D. J., Spurr, N., Stanier, P., Fisher, E. M., Nolan, P. M., Steel, K. P., Brown, S. D. M., Gray, I. C., Murdoch, J. N., & Orton, E. (2003). Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Current Biology, 13(13), 1129-1133. https://doi.org/10.1016/S0960-9822(03)00374-9

@article{8da5414e796642ccbee92ffd5fd26dff,

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 [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.",

keywords = "Animals, genetics: Cell Polarity, Chromosome Mapping, Comparative Study, physiopathology: Hair Cells, Inner, In Situ Hybridization, Mice, Microscopy, Electron, Scanning, genetics: Mutation, Missense, physiopathology: Neural Tube Defects, genetics: Receptors, G-Protein-Coupled, Research Support, Non-U.S. Gov't, Sequence Analysis, DNA, physiology: Signal Transduction",

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

year = "2003",

month = jul,

day = "1",

doi = "10.1016/S0960-9822(03)00374-9",

language = "English",

volume = "13",

pages = "1129--1133",

journal = "Current Biology",

issn = "0960-9822",

publisher = "Cell Press",

number = "13",

}

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 & Orton, E 2003, 'Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse', Current Biology, vol. 13, no. 13, pp. 1129-1133. https://doi.org/10.1016/S0960-9822(03)00374-9

TY - JOUR

T1 - Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse

AU - Curtin, John A.

AU - Quint, Elizabeth

AU - Tsipouri, Vicky

AU - Arkell, Ruth M.

AU - Cattanach, Bruce

AU - Copp, Andrew J.

AU - Henderson, Deborah J.

AU - Spurr, Nigel

AU - Stanier, Philip

AU - Fisher, Elizabeth M.

AU - Nolan, Patrick M.

AU - Steel, Karen P.

AU - Brown, Steve D M

AU - Gray, Ian C.

AU - Murdoch, Jennifer N.

AU - Orton, Elizabeth

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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.

AB - 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.

KW - Animals

KW - genetics: Cell Polarity

KW - Chromosome Mapping

KW - Comparative Study

KW - physiopathology: Hair Cells, Inner

KW - In Situ Hybridization

KW - Mice

KW - Microscopy, Electron, Scanning

KW - genetics: Mutation, Missense

KW - physiopathology: Neural Tube Defects

KW - genetics: Receptors, G-Protein-Coupled

KW - Research Support, Non-U.S. Gov't

KW - Sequence Analysis, DNA

KW - physiology: Signal Transduction

U2 - 10.1016/S0960-9822(03)00374-9

DO - 10.1016/S0960-9822(03)00374-9

M3 - Article

SN - 0960-9822

VL - 13

SP - 1129

EP - 1133

JO - Current Biology

JF - Current Biology

IS - 13

ER -

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

Abstract

Keywords

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