title: Functional antagonism of voltage-gated K+ channel α-subunits in the developing brain ventricular system.
abstract: The brain ventricular system is essential for neurogenesis and brain homeostasis. Its neuroepithelial lining effects these functions, but the underlying molecular pathways remain to be understood. We found that the potassium channels expressed in neuroepithelial cells determine the formation of the ventricular system. The phenotype of a novel zebrafish mutant characterized by denudation of neuroepithelial lining of the ventricular system and hydrocephalus is mechanistically linked to Kcng4b, a homologue of the 'silent' voltage-gated potassium channel α-subunit Kv6.4. We demonstrated that Kcng4b modulates proliferation of cells lining the ventricular system and maintains their integrity. The gain of Kcng4b function reduces the size of brain ventricles. Electrophysiological studies suggest that Kcng4b mediates its effects via an antagonistic interaction with Kcnb1, the homologue of the electrically active delayed rectifier potassium channel subunit Kv2.1. Mutation of kcnb1 reduces the size of the ventricular system and its gain of function causes hydrocephalus, which is opposite to the function of Kcng4b. This demonstrates the dynamic interplay between potassium channel subunits in the neuroepithelium as a novel and crucial regulator of ventricular development in the vertebrate brain.
authors.affiliation: Institute of Molecular and Cell Biology, Singapore.
authors.forename: Hongyuan
authors.identifier: 0000-0003-4043-7330
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department for Biomedical Sciences, University of Antwerp, Wilrijk B-2610, Belgium.
authors.forename: Elke
authors.identifier: 0000-0002-5005-8820
authors.initials: E
authors.lastname: Bocksteins
authors.affiliation: Institute of Molecular and Cell Biology, Singapore.
authors.forename: Igor
authors.identifier: 0000-0002-2268-7291
authors.initials: I
authors.lastname: Kondrychyn
authors.affiliation: Department for Biomedical Sciences, University of Antwerp, Wilrijk B-2610, Belgium.
authors.forename: Dirk
authors.identifier: 0000-0001-7142-6672
authors.initials: D
authors.lastname: Snyders
authors.affiliation: Institute of Molecular and Cell Biology, Singapore vlad@imcb.a-star.edu.sg.|Department of Biological Sciences, National University of Singapore, 117543, Singapore.
authors.forename: Vladimir
authors.identifier: 0000-0002-6580-7986
authors.initials: V
authors.lastname: Korzh
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics; D002552:Cerebral Ventricles / Q000196:embryology* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D006849:Hydrocephalus / Q000196:embryology / Q000235:genetics; D046569:Neuroepithelial Cells / Q000378:metabolism / Q000502:physiology; D038081:Organogenesis / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000502:physiology; D051669:Shab Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D050994:Voltage-Dependent Anion Channels / Q000235:genetics*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: C000622409:Kcnb1 protein, zebrafish; C000622408:Kcng4b protein, zebrafish; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D051669:Shab Potassium Channels; D050994:Voltage-Dependent Anion Channels; D029961:Zebrafish Proteins
keywords: Cell proliferation; Hydrocephalus; Kcnb1; Kcng4b; Neuroependyma extrusion; Tissue integrity; Zebrafish