Electrical signals polarize neuronal organelles, direct neuron migration, and orient cell division.
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.
Yao
Li
L
School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, United Kingdom.
McCaig
Colin D
CD
Zhao
Min
M
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D018385:Centrosome / Q000502:physiology; D004574:Electromagnetic Fields; D006056:Golgi Apparatus / Q000502:physiology; D020439:Growth Cones / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016501:Neurites / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D015388:Organelles / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054460:rho-Associated Kinases