PUBLICATION

The zebrafish ennui behavioral mutation disrupts acetylcholine receptor localization and motor axon stability

Authors
Saint-Amant, L., Sprague, S.M., Hirata, H., Li, Q., Cui, W.W., Zhou, W., Poudou, O., Hume, R.I., and Kuwada, J.Y.
ID
ZDB-PUB-071009-14
Date
2008
Source
Developmental Neurobiology   68(1): 45-61 (Journal)
Registered Authors
Cui, Wilson, Hirata, Hiromi, Kuwada, John, Li, Qin, Saint-Amant, Louis, Sprague, Shawn, Zhou, Weibin
Keywords
development, neuromuscular, mutant, acetylcholine, synapse
MeSH Terms
  • Action Potentials/drug effects
  • Action Potentials/genetics
  • Agrin/pharmacology
  • Animals
  • Axons/drug effects
  • Axons/physiology*
  • Behavior, Animal
  • Embryo, Nonmammalian
  • Motor Neurons/drug effects
  • Motor Neurons/pathology*
  • Movement Disorders*/genetics
  • Movement Disorders*/pathology
  • Movement Disorders*/physiopathology
  • Mutation/physiology*
  • Nerve Tissue Proteins/metabolism
  • Neuromuscular Junction/physiopathology
  • Protein Transport/drug effects
  • Receptors, Cholinergic/metabolism*
  • Swimming
  • Synaptic Transmission/drug effects
  • Synaptic Transmission/physiology
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
17918238 Full text @ Dev. Neurobiol.
Abstract
The zebrafish ennui mutation was identified from a mutagenesis screen for defects in early behavior. Homozygous ennui embryos swam more slowly than wild-type siblings but normal swimming recovered during larval stages and homozygous mutants survived until adulthood. Electrophysiological recordings from motoneurons and muscles suggested that the motor output of the CNS following mechanosensory stimulation was normal in ennui, but the synaptic currents at the neuromuscular junction were significantly reduced. Analysis of acetylcholine receptors (AChRs) in ennui muscles showed a marked reduction in the size of synaptic clusters and their aberrant localization at the myotome segment borders of fast twitch muscle. Prepatterned, nerve-independent AChR clusters appeared normal in mutant embryos and dispersed upon outgrowth of motor axons onto the muscles. Genetic mosaic analysis showed that ennui is required cell autonomously in muscle fibers for normal synaptic localization of AChRs. Furthermore, exogenous agrin failed to induce AChR aggregation, suggesting that ennui is crucial for agrin function. Finally, motor axons branched more extensively in ennui fast twitch muscles especially in the region of the myotome borders. These results suggest that ennui is important for nerve-dependent AChR clustering and the stability of axon growth.
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