title: Regulation of mitotic spindle orientation: an integrated view.
abstract: Mitotic spindle orientation is essential for cell fate decisions, epithelial maintenance, and tissue morphogenesis. In most animal cell types, the dynein motor complex is anchored at the cell cortex and exerts pulling forces on astral microtubules to position the spindle. Early studies identified the evolutionarily conserved Gαi/LGN/NuMA complex as a key regulator that polarizes cortical force generators. In recent years, a combination of genetics, biochemistry, modeling, and live imaging has contributed to decipher the mechanisms of spindle orientation. Here, we highlight the dynamic nature of the assembly of this complex and discuss the molecular regulation of its localization. Remarkably, a number of LGN-independent mechanisms were described recently, whereas NuMA remains central in most pathways involved in recruiting force generators at the cell cortex. We also describe the emerging role of the actin cortex in spindle orientation and discuss how dynamic astral microtubule formation is involved. We further give an overview on instructive external signals that control spindle orientation in tissues. Finally, we discuss the influence of cell geometry and mechanical forces on spindle orientation.
authors.affiliation: Cell Division and Neurogenesis Laboratory, Ecole Normale Supérieure CNRS Inserm Institut de Biologie de l'Ecole Normale Supérieure (IBENS) PSL Research University, Paris, France Institute of Doctoral Studies (IFD), Sorbonne Universités Université Pierre et Marie Curie-Université Paris 6, Paris, France.
authors.forename: Florencia
authors.initials: F
authors.lastname: di Pietro
authors.affiliation: Membrane Traffic and Cell Division Laboratory, Cell Biology and Infection Department, Institut Pasteur, Paris, France Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3691, Paris, France arnaud.echard@pasteur.fr xavier.morin@ens.fr.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Echard
authors.affiliation: Cell Division and Neurogenesis Laboratory, Ecole Normale Supérieure CNRS Inserm Institut de Biologie de l'Ecole Normale Supérieure (IBENS) PSL Research University, Paris, France arnaud.echard@pasteur.fr xavier.morin@ens.fr.
authors.forename: Xavier
authors.identifier: 0000-0001-9999-0355
authors.initials: X
authors.lastname: Morin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D002453:Cell Cycle; D004398:Dyneins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D046912:Multiprotein Complexes / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D021381:Protein Transport; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D000199:Actins; D046912:Multiprotein Complexes; D034521:Nuclear Matrix-Associated Proteins; D004398:Dyneins
keywords: NuMA; actin cortex; astral microtubules; cell geometry; spindle orientation