ZFIN ID: ZDB-PUB-161013-4
Functional antagonism of alpha-subunits of Kv channel in developing brain ventricular system
Shen, H., Bocksteins, E., Kondrychyn, I., Snyders, D., Korzh, V.
Date: 2016
Source: Development (Cambridge, England)   143(22): 4249-4260 (Journal)
Registered Authors: Kondrychyn, Igor, Korzh, Vladimir, Shen, Hongyuan
Keywords: Kcng4b, Kcnb1, Neuroependyma extrusion, hydrocephalus, Cell proliferation, Tissue integrity, Zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Brain/embryology*
  • Brain/metabolism
  • Cell Proliferation/genetics
  • Cerebral Ventricles/embryology*
  • Cerebral Ventricles/metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Hydrocephalus/embryology
  • Hydrocephalus/genetics
  • Neuroepithelial Cells/metabolism
  • Neuroepithelial Cells/physiology
  • Organogenesis*/genetics
  • Potassium Channels, Voltage-Gated/antagonists & inhibitors*
  • Potassium Channels, Voltage-Gated/genetics
  • Potassium Channels, Voltage-Gated/physiology*
  • Protein Subunits/antagonists & inhibitors
  • Protein Subunits/physiology
  • Shab Potassium Channels/antagonists & inhibitors
  • Shab Potassium Channels/physiology
  • Voltage-Dependent Anion Channels/genetics*
  • Zebrafish
  • Zebrafish Proteins/genetics*
PubMed: 27729411 Full text @ Development
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.