title: GEMC1 is a critical regulator of multiciliated cell differentiation.
abstract: The generation of multiciliated cells (MCCs) is required for the proper function of many tissues, including the respiratory tract, brain, and germline. Defects in MCC development have been demonstrated to cause a subclass of mucociliary clearance disorders termed reduced generation of multiple motile cilia (RGMC). To date, only two genes, Multicilin (MCIDAS) and cyclin O (CCNO) have been identified in this disorder in humans. Here, we describe mice lacking GEMC1 (GMNC), a protein with a similar domain organization as Multicilin that has been implicated in DNA replication control. We have found that GEMC1-deficient mice are growth impaired, develop hydrocephaly with a high penetrance, and are infertile, due to defects in the formation of MCCs in the brain, respiratory tract, and germline. Our data demonstrate that GEMC1 is a critical regulator of MCC differentiation and a candidate gene for human RGMC or related disorders.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Terré
authors.affiliation: FIRC Institute of Molecular Oncology, Milan, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Piergiovanni
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Segura-Bayona
authors.affiliation: IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gil-Gómez
authors.affiliation: Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Sameh A
authors.initials: SA
authors.lastname: Youssef
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Camille Stephan-Otto
authors.initials: CS
authors.lastname: Attolini
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Wilsch-Bräuninger
authors.affiliation: Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Carole
authors.initials: C
authors.lastname: Jung
authors.affiliation: Computational Biology and Bioinformatics Group, Institute of Biomedicine of Seville, Campus Hospital Universitario Virgen del Rocio, Seville, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rojas
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Marko
authors.initials: M
authors.lastname: Marjanović
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Knobel
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Palenzuela
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: López-Rovira
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Stephen
authors.initials: S
authors.lastname: Forrow
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Wieland B
authors.initials: WB
authors.lastname: Huttner
authors.affiliation: Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Valverde
authors.affiliation: Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Alain
authors.initials: A
authors.lastname: de Bruin
authors.affiliation: FIRC Institute of Molecular Oncology, Milan, Italy vincenzo.costanzo@ifom.eu travis.stracker@irbbarcelona.org.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Costanzo
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain vincenzo.costanzo@ifom.eu travis.stracker@irbbarcelona.org.
authors.forename: Travis H
authors.initials: TH
authors.lastname: Stracker
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002923:Cilia / Q000235:genetics* / Q000502:physiology*; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C000605589:Gmnc protein, mouse
keywords: cilia; ciliopathy; hydrocephaly; infertility; transcription