title: Celsr1 is required for the generation of polarity at multiple levels of the mouse oviduct.
abstract: The oviduct is an important organ in reproduction where fertilization occurs, and through which the fertilized eggs are carried to the uterus in mammals. This organ is highly polarized, where the epithelium forms longitudinal folds along the ovary-uterus axis, and the epithelial multicilia beat towards the uterus to transport the ovulated ova. Here, we analyzed the postnatal development of mouse oviduct and report that multilevel polarities of the oviduct are regulated by a planar cell polarity (PCP) gene, Celsr1. In the epithelium, Celsr1 is concentrated in the specific cellular boundaries perpendicular to the ovary-uterus axis from postnatal day 2. We found a new feature of cellular polarity in the oviduct - the apical surface of epithelial cells is elongated along the ovary-uterus axis. In Celsr1-deficient mice, the ciliary motion is not orchestrated along the ovary-uterus axis and the transport ability of beating cilia is impaired. Epithelial cells show less elongation and randomized orientation, and epithelial folds show randomized directionality and ectopic branches in the mutant. Our mosaic analysis suggests that the geometry of epithelial cells is primarily regulated by Celsr1 and as a consequence the epithelial folds are aligned. Taken together, we reveal the characteristics of the multilevel polarity formation processes in the mouse oviduct epithelium and suggest a novel function of the PCP pathway for proper tissue morphogenesis.
authors.affiliation: Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Shi
authors.affiliation: Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Komatsu
authors.affiliation: Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hirao
authors.affiliation: Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan The Graduate University for Advanced Studies, Okazaki, Aichi, 444-8787, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Toyooka
authors.affiliation: Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan The Graduate University for Advanced Studies, Okazaki, Aichi, 444-8787, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koyama
authors.affiliation: Institute of Neuroscience, University of Louvain Medical School, Brussels B1200, Belgium.
authors.forename: Fadel
authors.initials: F
authors.lastname: Tissir
authors.affiliation: Institute of Neuroscience, University of Louvain Medical School, Brussels B1200, Belgium.
authors.forename: André M
authors.initials: AM
authors.lastname: Goffinet
authors.affiliation: Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Uemura
authors.affiliation: Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan The Graduate University for Advanced Studies, Okazaki, Aichi, 444-8787, Japan fujimori@nibb.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujimori
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology; D002923:Cilia / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D005453:Fluorescence; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008863:Microspheres; D038081:Organogenesis / Q000502:physiology*; D010057:Oviducts / Q000196:embryology* / Q000648:ultrastructure; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C117380:Celsr1 protein, mouse; D017931:DNA Primers; D043562:Receptors, G-Protein-Coupled; D001973:Bromodeoxyuridine
keywords: Cell shape; Celsr1/Flamingo; Cilia; Epithelial morphogenesis; Oviduct; Planar cell polarity