Abstract
During mitotic division in the telencephalic proliferative ventricular zone (VZ), the nuclei of the neural precursors move basally away from the ventricular surface for DNA synthesis, and apically return to the surface for mitotic division; a process known as interkinetic migration or "to-and-fro" nuclear translocation. The cell, which remains attached to the ventricular surface, either continues cycling, or exits the cycle and migrates to the subventricular zone or the developing cortical plate. Although gap junctions/hemichannels are known to modulate DNA synthesis via Ca(2+) waves, the role of Ca(+) oscillations and the mechanism of nuclear translocation in the VZ precursors are unclear. Here, we provide evidence that, during apical nuclear migration, VZ precursors display dynamic spontaneous Ca(2+) transients, which depend on functional gap junctions/hemichannels via ATP release and Ca(2+)-mobilizing messenger diffusion. Furthermore, we found that blocking gap junctions/hemichannels or short hairpin RNA-mediated knockdown of Cx43 (connexin 43) retards the apically directed interkinetic nuclear migration accompanied with changes in the nuclear length/width ratio. In addition, we demonstrated that blocking functional gap junctions/hemichannels induces phosphorylation of small GTPase cdc42 in the VZ precursors. The basal phase of interkinetic migration is much slower and appears to be mediated passively by mechanical forces after cell division. Our findings indicate that functional interference with gap junctions/hemichannels during embryonic development may lead to abnormal corticogenesis and dysfunction of the cerebral cortex in adult organisms.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
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Adenosine Triphosphate / metabolism
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Adenosine Triphosphate / pharmacology
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Animals
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Boron Compounds / pharmacology
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Bromodeoxyuridine / metabolism
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Calcium / metabolism
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Calcium Signaling / drug effects
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Carbenoxolone / pharmacology
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Movement / physiology*
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism*
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Cerebral Ventricles / cytology
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Chelating Agents / pharmacology
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Connexin 43 / genetics
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Connexin 43 / metabolism
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Cyclooxygenase Inhibitors / pharmacology
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Embryo, Mammalian
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Female
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Gap Junctions / drug effects
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Gap Junctions / physiology*
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Ki-67 Antigen / metabolism
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Meclofenamic Acid / pharmacology
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Mice
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Neuroblastoma
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Neurons / drug effects
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Neurons / physiology
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Organ Culture Techniques
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Patch-Clamp Techniques / methods
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Platelet Aggregation Inhibitors / pharmacology
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Pregnancy
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Prosencephalon / cytology
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Pyridoxal Phosphate / analogs & derivatives
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Pyridoxal Phosphate / pharmacology
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Stem Cells / cytology*
Substances
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Boron Compounds
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Chelating Agents
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Connexin 43
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Cyclooxygenase Inhibitors
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Ki-67 Antigen
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Platelet Aggregation Inhibitors
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Green Fluorescent Proteins
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pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid
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Meclofenamic Acid
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Egtazic Acid
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Pyridoxal Phosphate
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Adenosine Triphosphate
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2-aminoethoxydiphenyl borate
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Bromodeoxyuridine
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Carbenoxolone
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
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Calcium