MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia

Mieke Boon; Julia Wallmeier; Lina Ma; Niki Tomas Loges; Martine Jaspers; Heike Olbrich; Gerard W. Dougherty; Johanna Raidt; Claudius Werner; Israel Amirav; Avigdor Hevroni; Revital Abitbul; Avraham Avital; Ruth Soferman; Marja Wessels; Christopher O'Callaghan; Eddie M.K. Chung; Andrew Rutman; Robert A. Hirst; Eduardo Moya; Hannah M. Mitchison; Sabine Van Daele; Kris De Boeck; Mark Jorissen; Chris Kintner; Harry Cuppens; Heymut Omran

doi:10.1038/ncomms5418

MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia

Mieke Boon, Julia Wallmeier, Lina Ma, Niki Tomas Loges, Martine Jaspers, Heike Olbrich, Gerard W. Dougherty, Johanna Raidt, Claudius Werner, Israel Amirav, Avigdor Hevroni, Revital Abitbul, Avraham Avital, Ruth Soferman, Marja Wessels, Christopher O'Callaghan, Eddie M.K. Chung, Andrew Rutman, Robert A. Hirst, Eduardo MoyaHannah M. Mitchison, Sabine Van Daele, Kris De Boeck, Mark Jorissen, Chris Kintner, Harry Cuppens, Heymut Omran

Bar-Ilan University - Azrieli Faculty of Medicine

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

200 Scopus citations

Abstract

Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary clearance disorder. Affected persons suffer from recurrent infections of upper and lower airways because of highly reduced numbers of multiple motile respiratory cilia. Here we report recessive loss-of-function and missense mutations in MCIDAS-encoding Multicilin, which was shown to promote the early steps of multiciliated cell differentiation in Xenopus. MCIDAS mutant respiratory epithelial cells carry only one or two cilia per cell, which lack ciliary motility-related proteins (DNAH5; CCDC39) as seen in primary ciliary dyskinesia. Consistent with this finding, FOXJ1-regulating axonemal motor protein expression is absent in respiratory cells of MCIDAS mutant individuals. CCNO, when mutated known to cause RGMC, is also absent in MCIDAS mutant respiratory cells, consistent with its downstream activity. Thus, our findings identify Multicilin as a key regulator of CCNO/FOXJ1 for human multiciliated cell differentiation, and highlight the 5q11 region containing CCNO and MCIDAS as a locus underlying RGMC.

Original language	English
Article number	4418
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5418
State	Published - 22 Jul 2014

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Boon, M., Wallmeier, J., Ma, L., Loges, N. T., Jaspers, M., Olbrich, H., Dougherty, G. W., Raidt, J., Werner, C., Amirav, I., Hevroni, A., Abitbul, R., Avital, A., Soferman, R., Wessels, M., O'Callaghan, C., Chung, E. M. K., Rutman, A., Hirst, R. A., ... Omran, H. (2014). MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia. Nature Communications, 5, Article 4418. https://doi.org/10.1038/ncomms5418

@article{8b42cd53ed2c4a54bc3972554fc7ed16,

title = "MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia",

abstract = "Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary clearance disorder. Affected persons suffer from recurrent infections of upper and lower airways because of highly reduced numbers of multiple motile respiratory cilia. Here we report recessive loss-of-function and missense mutations in MCIDAS-encoding Multicilin, which was shown to promote the early steps of multiciliated cell differentiation in Xenopus. MCIDAS mutant respiratory epithelial cells carry only one or two cilia per cell, which lack ciliary motility-related proteins (DNAH5; CCDC39) as seen in primary ciliary dyskinesia. Consistent with this finding, FOXJ1-regulating axonemal motor protein expression is absent in respiratory cells of MCIDAS mutant individuals. CCNO, when mutated known to cause RGMC, is also absent in MCIDAS mutant respiratory cells, consistent with its downstream activity. Thus, our findings identify Multicilin as a key regulator of CCNO/FOXJ1 for human multiciliated cell differentiation, and highlight the 5q11 region containing CCNO and MCIDAS as a locus underlying RGMC.",

author = "Mieke Boon and Julia Wallmeier and Lina Ma and Loges, {Niki Tomas} and Martine Jaspers and Heike Olbrich and Dougherty, {Gerard W.} and Johanna Raidt and Claudius Werner and Israel Amirav and Avigdor Hevroni and Revital Abitbul and Avraham Avital and Ruth Soferman and Marja Wessels and Christopher O'Callaghan and Chung, {Eddie M.K.} and Andrew Rutman and Hirst, {Robert A.} and Eduardo Moya and Mitchison, {Hannah M.} and {Van Daele}, Sabine and {De Boeck}, Kris and Mark Jorissen and Chris Kintner and Harry Cuppens and Heymut Omran",

year = "2014",

month = jul,

day = "22",

doi = "10.1038/ncomms5418",

language = "אנגלית",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

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Boon, M, Wallmeier, J, Ma, L, Loges, NT, Jaspers, M, Olbrich, H, Dougherty, GW, Raidt, J, Werner, C, Amirav, I, Hevroni, A, Abitbul, R, Avital, A, Soferman, R, Wessels, M, O'Callaghan, C, Chung, EMK, Rutman, A, Hirst, RA, Moya, E, Mitchison, HM, Van Daele, S, De Boeck, K, Jorissen, M, Kintner, C, Cuppens, H & Omran, H 2014, 'MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia', Nature Communications, vol. 5, 4418. https://doi.org/10.1038/ncomms5418

TY - JOUR

T1 - MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia

AU - Boon, Mieke

AU - Wallmeier, Julia

AU - Ma, Lina

AU - Loges, Niki Tomas

AU - Jaspers, Martine

AU - Olbrich, Heike

AU - Dougherty, Gerard W.

AU - Raidt, Johanna

AU - Werner, Claudius

AU - Amirav, Israel

AU - Hevroni, Avigdor

AU - Abitbul, Revital

AU - Avital, Avraham

AU - Soferman, Ruth

AU - Wessels, Marja

AU - O'Callaghan, Christopher

AU - Chung, Eddie M.K.

AU - Rutman, Andrew

AU - Hirst, Robert A.

AU - Moya, Eduardo

AU - Mitchison, Hannah M.

AU - Van Daele, Sabine

AU - De Boeck, Kris

AU - Jorissen, Mark

AU - Kintner, Chris

AU - Cuppens, Harry

AU - Omran, Heymut

PY - 2014/7/22

Y1 - 2014/7/22

N2 - Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary clearance disorder. Affected persons suffer from recurrent infections of upper and lower airways because of highly reduced numbers of multiple motile respiratory cilia. Here we report recessive loss-of-function and missense mutations in MCIDAS-encoding Multicilin, which was shown to promote the early steps of multiciliated cell differentiation in Xenopus. MCIDAS mutant respiratory epithelial cells carry only one or two cilia per cell, which lack ciliary motility-related proteins (DNAH5; CCDC39) as seen in primary ciliary dyskinesia. Consistent with this finding, FOXJ1-regulating axonemal motor protein expression is absent in respiratory cells of MCIDAS mutant individuals. CCNO, when mutated known to cause RGMC, is also absent in MCIDAS mutant respiratory cells, consistent with its downstream activity. Thus, our findings identify Multicilin as a key regulator of CCNO/FOXJ1 for human multiciliated cell differentiation, and highlight the 5q11 region containing CCNO and MCIDAS as a locus underlying RGMC.

AB - Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary clearance disorder. Affected persons suffer from recurrent infections of upper and lower airways because of highly reduced numbers of multiple motile respiratory cilia. Here we report recessive loss-of-function and missense mutations in MCIDAS-encoding Multicilin, which was shown to promote the early steps of multiciliated cell differentiation in Xenopus. MCIDAS mutant respiratory epithelial cells carry only one or two cilia per cell, which lack ciliary motility-related proteins (DNAH5; CCDC39) as seen in primary ciliary dyskinesia. Consistent with this finding, FOXJ1-regulating axonemal motor protein expression is absent in respiratory cells of MCIDAS mutant individuals. CCNO, when mutated known to cause RGMC, is also absent in MCIDAS mutant respiratory cells, consistent with its downstream activity. Thus, our findings identify Multicilin as a key regulator of CCNO/FOXJ1 for human multiciliated cell differentiation, and highlight the 5q11 region containing CCNO and MCIDAS as a locus underlying RGMC.

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DO - 10.1038/ncomms5418

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C2 - 25048963

AN - SCOPUS:84906274398

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4418

ER -

MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia

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