Abstract
Movement of meiosis I (MI) chromosomes from the oocyte centre to a subcortical location is the first step in the establishment of cortical polarity. This is required for two consecutive rounds of asymmetric meiotic cell divisions, which generate a mature egg and two polar bodies1. Here we use live-cell imaging and genetic and pharmacological manipulations to determine the force-generating mechanism underlying this chromosome movement. Chromosomes were observed to move toward the cortex in a pulsatile manner along a meandering path. This movement is not propelled by myosin-II-driven cortical flow but is associated with a cloud of dynamic actin filaments trailing behind the chromosomes/spindle. Formation of these filaments depends on the actin nucleation activity of Fmn2, a formin-family protein that concentrates around chromosomes through its amino-terminal region. Symmetry breaking of the actin cloud relative to chromosomes, and net chromosome translocation toward the cortex require actin turnover.
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Acknowledgements
We thank Roland Wedlich-Soldner (Max Plank Institute, Munich) for providing F-Lifeact peptide; Philip Leder (Harvard Medical School, Boston)) for Fmn2−/− mice and full-length Fmn2 cDNA; Marie-Helene Verlhac (Universite Paris VI, Paris) for pBluescript RN3 vector; Eric Jessen (Stowers Institute, Kansa City, applying to all persons mentioned hereafter) for help in site-directed mutagenesis; Rhonda Allen for electron microscopy; Xiaoxue Fan for help with actin preparation; Praveen Suraneni and Manqi Deng for help with the mouse work; Heather Marshall and Michael Durnin for training in oocyte dissection and microinjection; and Stowers Imaging Center for assistance with live imaging; Stacie Hughes for comments on the manuscript. This work was supported by funds to R.L. from the Stowers Institute for Medical Research.
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H.L. and R.L. designed the experiments, analysed the data and wrote the manuscript; H.L. performed all experiments except the electron microscopy and immuno-electron microscopy experiments, which were performed by F.G.; B.R. assisted with data and statistical analyses; R.L supervised the whole project.
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Li, H., Guo, F., Rubinstein, B. et al. Actin-driven chromosomal motility leads to symmetry breaking in mammalian meiotic oocytes. Nat Cell Biol 10, 1301–1308 (2008). https://doi.org/10.1038/ncb1788
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DOI: https://doi.org/10.1038/ncb1788
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