title: Sequential actin-based pushing forces drive meiosis I chromosome migration and symmetry breaking in oocytes.
abstract: Polar body extrusion during oocyte maturation is critically dependent on asymmetric positioning of the meiotic spindle, which is established through migration of the meiosis I (MI) spindle/chromosomes from the oocyte interior to a subcortical location. In this study, we show that MI chromosome migration is biphasic and driven by consecutive actin-based pushing forces regulated by two actin nucleators, Fmn2, a formin family protein, and the Arp2/3 complex. Fmn2 was recruited to endoplasmic reticulum structures surrounding the MI spindle, where it nucleated actin filaments to initiate an initially slow and poorly directed motion of the spindle away from the cell center. A fast and highly directed second migration phase was driven by actin-mediated cytoplasmic streaming and occurred as the chromosomes reach a sufficient proximity to the cortex to activate the Arp2/3 complex. We propose that decisive symmetry breaking in mouse oocytes results from Fmn2-mediated perturbation of spindle position and the positive feedback loop between chromosome signal-induced Arp2/3 activation and Arp2/3-orchestrated cytoplasmic streaming that transports the chromosomes.
authors: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors: Kexi
authors: K
authors: Yi
authors: Boris
authors: B
authors: Rubinstein
authors: Jay R
authors: JR
authors: Unruh
authors: Fengli
authors: F
authors: Guo
authors: Brian D
authors: BD
authors: Slaughter
authors: Rong
authors: R
authors: Li
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D020090:Chromosome Segregation; D003595:Cytoplasmic Streaming; D004721:Endoplasmic Reticulum / Q000378:metabolism; D025461:Feedback, Physiological; D005260:Female; D000080865:Formins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D049469:Meiotic Prophase I; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism*; D059705:Polar Bodies / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D013997:Time Factors; D059008:Time-Lapse Imaging; D014162:Transfection
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000080865:Formins; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C549436:formin 2 protein, mouse