title: Analysis and modeling of mitotic spindle orientations in three dimensions.
abstract: The orientation of the mitotic spindle determines the relative size and position of the daughter cells and influences the asymmetric inheritance of localized cell fate determinants. The onset of mammalian neurogenesis, for example, coincides with changes in spindle orientation. To address the functional implications of this and related phenomena, precise methods for determining the orientation of the mitotic spindle in complex tissues are needed. Here, we present methodology for the analysis of spindle orientation in 3D. Our method allows statistical analysis and modeling of spindle orientation and involves two parameters for horizontal and vertical bias that can unambiguously describe the distribution of spindle orientations in an experimental sample. We find that 3D analysis leads to systematically different results from 2D analysis and, surprisingly, truly random spindle orientations do not result in equal numbers of horizontal and vertical orientations. We show that our method can describe the distribution of spindle orientation angles under different biological conditions. As an example of biological application we demonstrate that the adapter protein Inscuteable (mInsc) can actively promote vertical spindle orientation in apical progenitors during mouse neurogenesis.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Jüschke
authors.forename: Yunli
authors.initials: Y
authors.lastname: Xie
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Postiglione
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Knoblich
mesh_terms: D000465:Algorithms; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division; D019070:Cell Lineage; D016764:Cell Polarity / Q000235:genetics; D003198:Computer Simulation; D021621:Imaging, Three-Dimensional; D051379:Mice; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011336:Probability; D008941:Spindle Apparatus; D013269:Stochastic Processes
chemical_list: D018797:Cell Cycle Proteins; C561632:inscuteable protein, mouse; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4