Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates

Alison J. Ross; Helen May-Simera; Erica R. Eichers; Masatake Kai; Josephine Hill; Daniel J. Jagger; Carmen C. Leitch; J. Paul Chapple; Peter M. Munro; Shannon Fisher; Perciliz L. Tan; Helen M. Phillips; Michel R. Leroux; Deborah J. Henderson; Jennifer N. Murdoch; Andrew J. Copp; Marie Madeleine Eliot; James R. Lupski; David T. Kemp; Hélène Dollfus; Masazumi Tada; Elias Nicholas Katsanis; Andrew Forge; Philip L. Beales

doi:10.1038/ng1644

Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates

Alison J. Ross, Helen May-Simera, Erica R. Eichers, Masatake Kai, Josephine Hill, Daniel J. Jagger, Carmen C. Leitch, J. Paul Chapple, Peter M. Munro, Shannon Fisher, Perciliz L. Tan, Helen M. Phillips, Michel R. Leroux, Deborah J. Henderson, Jennifer N. Murdoch, Andrew J. Copp, Marie Madeleine Eliot, James R. Lupski, David T. Kemp, Hélène DollfusMasazumi Tada, Elias Nicholas Katsanis, Andrew Forge, Philip L. Beales

Pediatrics

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

460 Scopus citations

Abstract

The evolutionarily conserved planar cell polarity (PCP) pathway (or noncanonical Wnt pathway) drives several important cellular processes, including epithelial cell polarization, cell migration and mitotic spindle orientation. In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation. Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction, share phenotypes with PCP mutants including open eyelids, neural tube defects and disrupted cochlear stereociliary bundles. Furthermore, we identify genetic interactions between BBS genes and a PCP gene in both mouse (Ltap, also called Vangl2) and zebrafish (vangl2). In zebrafish, the augmented phenotype results from enhanced defective convergent extension movements. We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of that of the BBS proteins. These data suggest that cilia are intrinsically involved in PCP processes.

Original language	English (US)
Pages (from-to)	1135-1140
Number of pages	6
Journal	Nature Genetics
Volume	37
Issue number	10
DOIs	https://doi.org/10.1038/ng1644
State	Published - Oct 2005

ASJC Scopus subject areas

Genetics

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Ross, A. J., May-Simera, H., Eichers, E. R., Kai, M., Hill, J., Jagger, D. J., Leitch, C. C., Chapple, J. P., Munro, P. M., Fisher, S., Tan, P. L., Phillips, H. M., Leroux, M. R., Henderson, D. J., Murdoch, J. N., Copp, A. J., Eliot, M. M., Lupski, J. R., Kemp, D. T., ... Beales, P. L. (2005). Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nature Genetics, 37(10), 1135-1140. https://doi.org/10.1038/ng1644

Ross, Alison J. ; May-Simera, Helen ; Eichers, Erica R. ; Kai, Masatake ; Hill, Josephine ; Jagger, Daniel J. ; Leitch, Carmen C. ; Chapple, J. Paul ; Munro, Peter M. ; Fisher, Shannon ; Tan, Perciliz L. ; Phillips, Helen M. ; Leroux, Michel R. ; Henderson, Deborah J. ; Murdoch, Jennifer N. ; Copp, Andrew J. ; Eliot, Marie Madeleine ; Lupski, James R. ; Kemp, David T. ; Dollfus, Hélène ; Tada, Masazumi ; Katsanis, Elias Nicholas ; Forge, Andrew ; Beales, Philip L. / Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. In: Nature Genetics. 2005 ; Vol. 37, No. 10. pp. 1135-1140.

@article{b40463964c1f4ba7912fd0f08bb89fe9,

title = "Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates",

abstract = "The evolutionarily conserved planar cell polarity (PCP) pathway (or noncanonical Wnt pathway) drives several important cellular processes, including epithelial cell polarization, cell migration and mitotic spindle orientation. In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation. Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction, share phenotypes with PCP mutants including open eyelids, neural tube defects and disrupted cochlear stereociliary bundles. Furthermore, we identify genetic interactions between BBS genes and a PCP gene in both mouse (Ltap, also called Vangl2) and zebrafish (vangl2). In zebrafish, the augmented phenotype results from enhanced defective convergent extension movements. We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of that of the BBS proteins. These data suggest that cilia are intrinsically involved in PCP processes.",

author = "Ross, {Alison J.} and Helen May-Simera and Eichers, {Erica R.} and Masatake Kai and Josephine Hill and Jagger, {Daniel J.} and Leitch, {Carmen C.} and Chapple, {J. Paul} and Munro, {Peter M.} and Shannon Fisher and Tan, {Perciliz L.} and Phillips, {Helen M.} and Leroux, {Michel R.} and Henderson, {Deborah J.} and Murdoch, {Jennifer N.} and Copp, {Andrew J.} and Eliot, {Marie Madeleine} and Lupski, {James R.} and Kemp, {David T.} and H{\'e}l{\`e}ne Dollfus and Masazumi Tada and Katsanis, {Elias Nicholas} and Andrew Forge and Beales, {Philip L.}",

note = "Funding Information: We thank P. Scambler, D. Savery, N. Greene, H. Omran, N. Guo and J. Nathans for their technical help and comments in preparing this manuscript. This study was supported by grants from the Wellcome Trust (A.J.R., J.H. and A.J.C.), Medical Research Council (H.M.-S., M.T. and J.N.M.), Birth Defects Foundation (J.H.), Defeating Deafness (A.F.), the National Institute of Child Health and Development and National Institute of Diabetes, Digestive and Kidney Disorders (US National Institutes of Health; N.K.) and British Heart Foundation (D.J.H. and H.M.P.). M.R.L acknowledges funding from Heart and Stroke Foundation of BC & Yukon and Canadian Institutes of Health Research and scholarships from Michael Smith Foundation for Health Research and Canadian Institutes of Health Research. P.L.B. is a Wellcome Trust Senior Research Fellow.",

year = "2005",

month = oct,

doi = "10.1038/ng1644",

language = "English (US)",

volume = "37",

pages = "1135--1140",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "10",

}

Ross, AJ, May-Simera, H, Eichers, ER, Kai, M, Hill, J, Jagger, DJ, Leitch, CC, Chapple, JP, Munro, PM, Fisher, S, Tan, PL, Phillips, HM, Leroux, MR, Henderson, DJ, Murdoch, JN, Copp, AJ, Eliot, MM, Lupski, JR, Kemp, DT, Dollfus, H, Tada, M, Katsanis, EN, Forge, A & Beales, PL 2005, 'Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates', Nature Genetics, vol. 37, no. 10, pp. 1135-1140. https://doi.org/10.1038/ng1644

Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. / Ross, Alison J.; May-Simera, Helen; Eichers, Erica R.; Kai, Masatake; Hill, Josephine; Jagger, Daniel J.; Leitch, Carmen C.; Chapple, J. Paul; Munro, Peter M.; Fisher, Shannon; Tan, Perciliz L.; Phillips, Helen M.; Leroux, Michel R.; Henderson, Deborah J.; Murdoch, Jennifer N.; Copp, Andrew J.; Eliot, Marie Madeleine; Lupski, James R.; Kemp, David T.; Dollfus, Hélène; Tada, Masazumi; Katsanis, Elias Nicholas; Forge, Andrew; Beales, Philip L.

In: Nature Genetics, Vol. 37, No. 10, 10.2005, p. 1135-1140.

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

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T1 - Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates

AU - Ross, Alison J.

AU - May-Simera, Helen

AU - Eichers, Erica R.

AU - Kai, Masatake

AU - Hill, Josephine

AU - Jagger, Daniel J.

AU - Leitch, Carmen C.

AU - Chapple, J. Paul

AU - Munro, Peter M.

AU - Fisher, Shannon

AU - Tan, Perciliz L.

AU - Phillips, Helen M.

AU - Leroux, Michel R.

AU - Henderson, Deborah J.

AU - Murdoch, Jennifer N.

AU - Copp, Andrew J.

AU - Eliot, Marie Madeleine

AU - Lupski, James R.

AU - Kemp, David T.

AU - Dollfus, Hélène

AU - Tada, Masazumi

AU - Katsanis, Elias Nicholas

AU - Forge, Andrew

AU - Beales, Philip L.

N1 - Funding Information: We thank P. Scambler, D. Savery, N. Greene, H. Omran, N. Guo and J. Nathans for their technical help and comments in preparing this manuscript. This study was supported by grants from the Wellcome Trust (A.J.R., J.H. and A.J.C.), Medical Research Council (H.M.-S., M.T. and J.N.M.), Birth Defects Foundation (J.H.), Defeating Deafness (A.F.), the National Institute of Child Health and Development and National Institute of Diabetes, Digestive and Kidney Disorders (US National Institutes of Health; N.K.) and British Heart Foundation (D.J.H. and H.M.P.). M.R.L acknowledges funding from Heart and Stroke Foundation of BC & Yukon and Canadian Institutes of Health Research and scholarships from Michael Smith Foundation for Health Research and Canadian Institutes of Health Research. P.L.B. is a Wellcome Trust Senior Research Fellow.

PY - 2005/10

Y1 - 2005/10

N2 - The evolutionarily conserved planar cell polarity (PCP) pathway (or noncanonical Wnt pathway) drives several important cellular processes, including epithelial cell polarization, cell migration and mitotic spindle orientation. In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation. Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction, share phenotypes with PCP mutants including open eyelids, neural tube defects and disrupted cochlear stereociliary bundles. Furthermore, we identify genetic interactions between BBS genes and a PCP gene in both mouse (Ltap, also called Vangl2) and zebrafish (vangl2). In zebrafish, the augmented phenotype results from enhanced defective convergent extension movements. We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of that of the BBS proteins. These data suggest that cilia are intrinsically involved in PCP processes.

AB - The evolutionarily conserved planar cell polarity (PCP) pathway (or noncanonical Wnt pathway) drives several important cellular processes, including epithelial cell polarization, cell migration and mitotic spindle orientation. In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation. Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction, share phenotypes with PCP mutants including open eyelids, neural tube defects and disrupted cochlear stereociliary bundles. Furthermore, we identify genetic interactions between BBS genes and a PCP gene in both mouse (Ltap, also called Vangl2) and zebrafish (vangl2). In zebrafish, the augmented phenotype results from enhanced defective convergent extension movements. We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of that of the BBS proteins. These data suggest that cilia are intrinsically involved in PCP processes.

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