title: CFAP157 is a murine downstream effector of FOXJ1 that is specifically required for flagellum morphogenesis and sperm motility.
abstract: Motile cilia move extracellular fluids or mediate cellular motility. Their function is essential for embryonic development, adult tissue homeostasis and reproduction throughout vertebrates. FOXJ1 is a key transcription factor for the formation of motile cilia but its downstream genetic programme is only partially understood. Here, we characterise a novel FOXJ1 target, Cfap157, that is specifically expressed in motile ciliated tissues in mouse and Xenopus in a FOXJ1-dependent manner. CFAP157 protein localises to basal bodies and interacts with tubulin and the centrosomal protein CEP350. Cfap157 knockout mice appear normal but homozygous males are infertile. Spermatozoa display impaired motility and a novel phenotype: Cfap157-deficient sperm exhibit axonemal loops, supernumerary axonemal profiles with ectopic accessory structures, excess cytoplasm and clustered mitochondria in the midpiece regions, and defective axonemes along the flagella. Our study thus demonstrates an essential sperm-specific function for CFAP157 and suggests that this novel FOXJ1 effector is part of a mechanism that acts during spermiogenesis to suppress the formation of supernumerary axonemes and ensures a correct ultrastructure.
authors.affiliation: Institute for Molecular Biology, OE5250, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Weidemann
authors.affiliation: Institute for Molecular Biology, OE5250, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Schuster-Gossler
authors.affiliation: Institute for Molecular Biology, OE5250, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stauber
authors.affiliation: Institute of Functional and Applied Anatomy, OE8840, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wrede
authors.affiliation: Institute of Functional and Applied Anatomy, OE8840, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hegermann
authors.affiliation: Institute of Zoology, University of Hohenheim, Garbenstraße 30, Stuttgart 70593, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Ott
authors.affiliation: Institute of Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Röntgenweg 11, Tübingen 72076, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Boldt
authors.affiliation: Institute of Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Röntgenweg 11, Tübingen 72076, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Beyer
authors.affiliation: Institute for Molecular Biology, OE5250, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Serth
authors.affiliation: Institute of Molecular Immunology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Core Facility Monoclonal Antibodies, Marchioninistr. 25, München 81377, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.affiliation: Institute of Zoology, University of Hohenheim, Garbenstraße 30, Stuttgart 70593, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Blum
authors.affiliation: Institute of Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Röntgenweg 11, Tübingen 72076, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
authors.affiliation: Institute for Molecular Biology, OE5250, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany gossler.achim@mh-hannover.de.
authors.forename: Achim
authors.identifier: 0000-0002-9103-9116
authors.initials: A
authors.lastname: Gossler
mesh_terms: D000818:Animals; D054468:Axoneme / Q000378:metabolism*; D064652:Basal Bodies / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005407:Flagella / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology; D013081:Sperm Motility / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014982:Xenopus laevis
chemical_list: C000622403:CFAP157 protein, mouse; D003598:Cytoskeletal Proteins; C481963:FOXJ1 protein, mouse; D051858:Forkhead Transcription Factors
keywords: Axoneme; Cfap157; Ciliogenesis; Male infertility; Spermiogenesis