Electrical signals polarize neuronal organelles, direct neuron migration, and orient cell division

Authors

  • Li Yao,

    1. School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, United Kingdom
    2. National Center for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
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  • Colin D. McCaig,

    Corresponding author
    1. School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, United Kingdom
    • School of Medical Sciences, University of Aberdeen Aberdeen AB25 2ZD, Scotland, UK
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  • Min Zhao

    Corresponding author
    1. School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, United Kingdom
    2. Department of Dermatology, University of California Davis, School of Medicine, California, CA 95618
    • Room 612D, Dermatology, Center for Neuroscience, UC Davis, School of Medicine, 1515 Newton Ct., Davis, CA 95618-4859, USA
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Abstract

During early brain development, the axis of division of neuronal precursor cells is regulated tightly and can determine whether neurons remain in the germinal layers or migrate away. Directed neuronal migration depends on the establishment of cell polarity, and cells are polarized dynamically in response to extracellular signals. Endogenous electric fields (EFs) orient cell division and direct migration of a variety of cell types. Here, we show that cell division of cultured hippocampal cells (neuron-like cells and glial-like cells) is oriented strikingly by an applied EF, which also directs neuronal migration. Directed migration involves polarization of the leading neurite, of the microtubule-associated protein MAP-2 and of the Golgi apparatus and the centrosome, all of which reposition asymmetrically to face the cathode. Pharmacological inhibition of Rho-associated coiled-coil forming protein kinases (ROCK) and phosphoinositide 3-kinase decreased, leading neurite orientation and Golgi polarization in the neurons in response to an EF and in parallel decreased the directedness of EF-guided neuronal migration. This work demonstrates that the axis of hippocampal cell division, the establishment of neuronal polarity, the polarization of intracellular structures, and the direction of neuronal migration are all regulated by an extracellular electrical cue. © 2009 Wiley-Liss, Inc.

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