title: Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair.
abstract: Morphogenesis, homeostasis, and regeneration of epithelial tissues rely on the accurate orientation of cell divisions, which is specified by the mitotic spindle axis. To remain in the epithelial plane, symmetrically dividing epithelial cells align their mitotic spindle axis with the plane. Here, we show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading to severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central regulatory mechanism of mitotic spindle orientation necessary for the alignment of epithelial cell divisions with the epithelial plane.
authors.affiliation: Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Jakub M
authors.initials: JM
authors.lastname: Swiercz
authors.affiliation: Centro de Biología Molecular Severo Ochoa, 28049 Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Bañón-Rodríguez
authors.affiliation: Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, 35043 Marburg, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Matković
authors.affiliation: Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Federico
authors.affiliation: Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Tianliang
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Franz
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Cord H
authors.initials: CH
authors.lastname: Brakebusch
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Roland H
authors.initials: RH
authors.lastname: Friedel
authors.affiliation: Centro de Biología Molecular Severo Ochoa, 28049 Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Martín-Belmonte
authors.affiliation: Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.affiliation: Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany; Medical Faculty, University of Frankfurt, 60590 Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.affiliation: Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany; Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, 35043 Marburg, Germany. Electronic address: thomas.worzfeld@staff.uni-marburg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Worzfeld
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000235:genetics; D002455:Cell Division / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D007668:Kidney / Q000196:embryology / Q000378:metabolism*; D008297:Male; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; D039961:Semaphorins; C091529:plexin