title: A new model for asymmetric spindle positioning in mouse oocytes.
abstract: An oocyte matures into an egg by extruding half of the chromosomes in a small polar body. This extremely asymmetric division enables the oocyte to retain sufficient storage material for the development of the embryo after fertilization. To divide asymmetrically, mammalian oocytes relocate the spindle from their center to the cortex. In all mammalian species analyzed so far, including human, mouse, cow, pig, and hamster, spindle relocation depends on filamentous actin (F-actin). However, even though spindle relocation is essential for fertility, the involved F-actin structures and the mechanism by which they relocate the spindle are unknown. Here we show in live mouse oocytes that spindle relocation requires a continuously reorganizing cytoplasmic actin network nucleated by Formin-2 (Fmn2). We found that the spindle poles were enriched in activated myosin and pulled on this network. Inhibition of myosin activation by myosin light chain kinase (MLCK) stopped pulling and spindle relocation, indicating that myosin pulling creates the force that drives spindle movement. Based on these results, we propose the first mechanistic model for asymmetric spindle positioning in mammalian oocytes and validate five of its key predictions experimentally.
authors.affiliation: European Molecular Biology Laboratory (EMBL), Gene Expression Unit, Heidelberg, Germany.
authors.forename: Melina
authors.initials: M
authors.lastname: Schuh
authors.forename: Jan
authors.initials: J
authors.lastname: Ellenberg
mesh_terms: D000199:Actins / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D005260:Female; D008540:Meiosis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009068:Movement / Q000502:physiology; D009218:Myosins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009865:Oocytes / Q000254:growth & development / Q000502:physiology* / Q000648:ultrastructure*; D009866:Oogenesis / Q000502:physiology; D008941:Spindle Apparatus / Q000502:physiology
chemical_list: D000199:Actins; D009419:Nerve Tissue Proteins; D009218:Myosins