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First published online September 22, 2005
doi: 10.1242/10.1242/jcs.02586


Journal of Cell Science 118, 4563-4575 (2005)
Published by The Company of Biologists 2005
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Research Article

An increase in [Ca2+]i is sufficient but not necessary for driving mitosis in early mouse embryos

Greg FitzHarris*, Mark Larman{ddagger}, Chris Richards and John Carroll§

Department of Physiology, University College London, Gower Street, London, WC1E 6BT, UK

§ Author for correspondence (e-mail: j.carroll{at}ucl.ac.uk)

Accepted 5 July 2005

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.

Key words: Ca2+ transient, Mitosis, Inositol (1,4,5)-trisphosphate, Two-photon microscopy







© The Company of Biologists Ltd 2005