title: An increase in [Ca2+]i is sufficient but not necessary for driving mitosis in early mouse embryos.
abstract: An increase in intracellular Ca2+ concentration ([Ca2+]i) has been shown to drive sea-urchin embryos and some fibroblasts through nuclear-envelope breakdown (NEBD) and the metaphase-to-anaphase transition. Mitotic Ca2+ transients can be pan-cellular global events or localized to the perinuclear region. It is not known whether Ca2+ is a universal regulator of mitosis or whether its role is confined to specific cell types. To test the hypothesis that Ca2+ is a universal regulator of mitosis, we have investigated the role of Ca2+ in mitosis in one-cell mouse embryos. Fertilized embryos generate Ca2+ transients during the first mitotic division. Imposing a Ca2+ transient by photorelease of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] resulted in acceleration of mitosis entry, suggesting that a [Ca2+]i increase is capable of triggering mitosis. Mitotic Ca2+ transients were inhibited using three independent approaches: injection of intracellular Ca2+ buffers; downregulation of Ins(1,4,5)P3 receptors; and removal of extracellular Ca2+. None of the interventions had any effects on the timing of NEBD or cytokinesis. The possibility that NEBD is driven by localized perinuclear Ca2+ transients was examined using two-photon microscopy but no Ca2+-dependent increases in fluorescence were found to precede NEBD. Finally, the second mitotic division took place in the absence of any detectable [Ca2+]i increase. Thus, although an induced [Ca2+]i increase can accelerate mitosis entry, neither cytosolic nor perinuclear [Ca2+] increases appear to be necessary for progression through mitosis in mouse embryos.
authors.affiliation: Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Greg
authors.initials: G
authors.lastname: FitzHarris
authors.forename: Mark
authors.initials: M
authors.lastname: Larman
authors.forename: Chris
authors.initials: C
authors.lastname: Richards
authors.forename: John
authors.initials: J
authors.lastname: Carroll
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology* / Q000502:physiology*; D005260:Female; D005306:Fertilization / Q000502:physiology; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D016257:Fura-2 / Q000737:chemistry / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000737:chemistry / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D008845:Microinjections; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D002614:Chelating Agents; D005456:Fluorescent Dyes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D016257:Fura-2