title: Cluap1 localizes preferentially to the base and tip of cilia and is required for ciliogenesis in the mouse embryo.
abstract: Qilin is one of several genes in zebrafish whose mutation results in cystic kidney. We have now studied the role of its mouse ortholog, Cluap1, in embryonic development by generating Cluap1 knockout (Cluap1-/-) mice. Cluap1-/- embryos died mid-gestation manifesting impairment of ciliogenesis in various regions including the node and neural tube. The basal body was found to be properly docked to the apical membrane of cells in the mutant, but the axoneme failed to grow. Cluap1 is a ciliary protein and is preferentially localized at the base and tip of cilia. Hedgehog signaling, as revealed with a Pacthed1-lacZ reporter gene, was lost in Cluap1-/- embryos at embryonic day (E) 8.5 but was ectopically expanded at E9.0. The Cluap1 knockout embryos also failed to manifest left-right asymmetric expression of Nodal in the lateral plate, most likely as a result of the loss of Hedgehog signaling in node crown cells that in turn leads to pronounced down-regulation of Gdf1 expression in these cells. Crown cell-specific restoration of Cluap1 expression rescued Gdf1 expression in crown cells and left-sided Nodal expression in the lateral plate of mutant embryos. Our results suggest that Cluap1 contributes to ciliogenesis by regulating the intraflagellar transport (IFT) cycle at the base and tip of the cilium.
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yanick
authors.initials: Y
authors.lastname: Botilde
authors.forename: Satoko
authors.initials: S
authors.lastname: Yoshiba
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Shinohara
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nishimura
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Shiratori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
mesh_terms: D000818:Animals; D019521:Body Patterning; D002923:Cilia / Q000378:metabolism*; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005838:Genotype; D053823:Hedgehog Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D007763:Lac Operon; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics*; D009154:Mutation; D015398:Signal Transduction
chemical_list: C583954:Cluap1 protein, mouse; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins
keywords: Cilia; Hedgehog signaling; Left–right asymmetry; Node