title: Dlg1 controls planar spindle orientation in the neuroepithelium through direct interaction with LGN.
abstract: Oriented cell divisions are necessary for the development of epithelial structures. Mitotic spindle orientation requires the precise localization of force generators at the cell cortex via the evolutionarily conserved LGN complex. However, polarity cues acting upstream of this complex in vivo in the vertebrate epithelia remain unknown. In this paper, we show that Dlg1 is localized at the basolateral cell cortex during mitosis and is necessary for planar spindle orientation in the chick neuroepithelium. Live imaging revealed that Dlg1 is required for directed spindle movements during metaphase. Mechanistically, we show that direct interaction between Dlg1 and LGN promotes cortical localization of the LGN complex. Furthermore, in human cells dividing on adhesive micropatterns, homogenously localized Dlg1 recruited LGN to the mitotic cortex and was also necessary for proper spindle orientation. We propose that Dlg1 acts primarily to recruit LGN to the cortex and that Dlg1 localization may additionally provide instructive cues for spindle orientation.
authors.affiliation: Institut de Biologie de l'École Normale Supérieure, Ecole Normale Supérieure, F-75005 Paris, France Institut National de la Santé et de la Recherche Medicale, U1024, F-75005 Paris, France Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8197, F-75005 Paris, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Saadaoui
authors.affiliation: Membrane Traffic and Cell Division Laboratory, Institut Pasteur, F-75015 Paris, France Centre National de la Recherche Scientifique, Unité de Recherche Associée 2582, F-75015 Paris, France Cellule Pasteur-Université Pierre et Marie Curie, Université Pierre et Marie Curie, F-75015 Paris, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Machicoane
authors.affiliation: Institut de Biologie de l'École Normale Supérieure, Ecole Normale Supérieure, F-75005 Paris, France Institut National de la Santé et de la Recherche Medicale, U1024, F-75005 Paris, France Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8197, F-75005 Paris, France Institute of Doctoral Studies (IFD), Sorbonne Universités, Université Pierre et Marie Curie-Université Paris 6, F-75252 Paris, France.
authors.forename: Florencia
authors.initials: F
authors.lastname: di Pietro
authors.affiliation: Institut de Biologie de l'École Normale Supérieure, Ecole Normale Supérieure, F-75005 Paris, France Institut National de la Santé et de la Recherche Medicale, U1024, F-75005 Paris, France Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8197, F-75005 Paris, France.
authors.forename: Fred
authors.initials: F
authors.lastname: Etoc
authors.affiliation: Membrane Traffic and Cell Division Laboratory, Institut Pasteur, F-75015 Paris, France Centre National de la Recherche Scientifique, Unité de Recherche Associée 2582, F-75015 Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Echard
authors.affiliation: Institut de Biologie de l'École Normale Supérieure, Ecole Normale Supérieure, F-75005 Paris, France Institut National de la Santé et de la Recherche Medicale, U1024, F-75005 Paris, France Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8197, F-75005 Paris, France xavier.morin@ens.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Morin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000235:genetics*; D002642:Chick Embryo; D000074288:Discs Large Homolog 1 Protein; D004848:Epithelium / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008938:Mitosis; D034622:RNA Interference; D034741:RNA, Small Interfering; D008941:Spindle Apparatus / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; C102754:GPSM2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering