title: Mitotic spindle asymmetry: a Wnt/PCP-regulated mechanism generating asymmetrical division in cortical precursors.
abstract: The regulation of asymmetric cell division (ACD) during corticogenesis is incompletely understood. We document that spindle-size asymmetry (SSA) between the two poles occurs during corticogenesis and parallels ACD. SSA appears at metaphase and is maintained throughout division, and we show it is necessary for proper neurogenesis. Imaging of spindle behavior and division outcome reveals that neurons preferentially arise from the larger-spindle pole. Mechanistically, SSA magnitude is controlled by Wnt7a and Vangl2, both members of the Wnt/planar cell polarity (PCP)-signaling pathway, and relayed to the cell cortex by P-ERM proteins. In vivo, Vangl2 and P-ERM downregulation promotes early cell-cycle exit and prevents the proper generation of late-born neurons. Thus, SSA is a core component of ACD that is conserved in invertebrates and vertebrates and plays a key role in the tight spatiotemporal control of self-renewal and differentiation during mammalian corticogenesis.
authors.affiliation: Stem Cell and Brain Research Institute, Institut National de la Santé et de la Recherche Médicale, U846, 18 Avenue Doyen Lépine, 69500 Bron, France; Université de Lyon, Université Lyon I, 69003 Lyon, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Delaunay
authors.affiliation: Stem Cell and Brain Research Institute, Institut National de la Santé et de la Recherche Médicale, U846, 18 Avenue Doyen Lépine, 69500 Bron, France; Université de Lyon, Université Lyon I, 69003 Lyon, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Cortay
authors.affiliation: Stem Cell and Brain Research Institute, Institut National de la Santé et de la Recherche Médicale, U846, 18 Avenue Doyen Lépine, 69500 Bron, France; Université de Lyon, Université Lyon I, 69003 Lyon, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Patti
authors.affiliation: Stem Cell and Brain Research Institute, Institut National de la Santé et de la Recherche Médicale, U846, 18 Avenue Doyen Lépine, 69500 Bron, France; Université de Lyon, Université Lyon I, 69003 Lyon, France.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Knoblauch
authors.affiliation: Stem Cell and Brain Research Institute, Institut National de la Santé et de la Recherche Médicale, U846, 18 Avenue Doyen Lépine, 69500 Bron, France; Université de Lyon, Université Lyon I, 69003 Lyon, France. Electronic address: colette.dehay@inserm.fr.
authors.forename: Colette
authors.initials: C
authors.lastname: Dehay
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D016764:Cell Polarity; D051379:Mice; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse