PUBLICATION

Functional antagonism of alpha-subunits of Kv channel in developing brain ventricular system

Authors
Shen, H., Bocksteins, E., Kondrychyn, I., Snyders, D., Korzh, V.
ID
ZDB-PUB-161013-4
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
  • Shab Potassium Channels/antagonists & inhibitors
  • Shab Potassium Channels/physiology
  • Potassium Channels, Voltage-Gated/antagonists & inhibitors*
  • Potassium Channels, Voltage-Gated/genetics
  • Potassium Channels, Voltage-Gated/physiology*
  • Animals
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Protein Subunits/antagonists & inhibitors
  • Protein Subunits/physiology
  • Neuroepithelial Cells/metabolism
  • Neuroepithelial Cells/physiology
  • Cell Proliferation/genetics
  • Organogenesis*/genetics
  • Hydrocephalus/embryology
  • Hydrocephalus/genetics
  • Zebrafish Proteins/genetics*
  • Cerebral Ventricles/embryology*
  • Cerebral Ventricles/metabolism
  • Zebrafish
  • Brain/embryology*
  • Brain/metabolism
  • Voltage-Dependent Anion Channels/genetics*
  • Animals, Genetically Modified
(all 24)
PubMed
27729411 Full text @ Development
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.
Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
kcnb1CRISPR1-kcnb1CRISPR
kcng4bMO1-kcng4bMRPHLNO
1 - 2 of 2
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Fish
Fish
AB
AB + MO1-kcng4b
kca6Tg
kca6Tg + MO1-kcng4b
kcnb1sq301/sq301
kcng4bsq300Gt/sq300Gt
kcng4bsq300Gt/+
WT
1 - 8 of 8
Show
Antibodies
Orthology
No data available
Engineered Foreign Genes
Marker Marker Type Name
GFPEFGGFP
1 - 1 of 1
Show
Mapping
No data available
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Citation
Shen, H., Bocksteins, E., Kondrychyn, I., Snyders, D., Korzh, V. (2016) Functional antagonism of alpha-subunits of Kv channel in developing brain ventricular system. Development (Cambridge, England). 143(22):4249-4260.