ZFIN ID: ZDB-PUB-151002-1
Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a
Yelin-Bekerman, L., Elbaz, I., Diber, A., Dahary, D., Gibbs-Bar, L., Alon, S., Lerer-Goldshtein, T., Appelbaum, L.
Date: 2015
Source: eLIFE   4: e08638 (Journal)
Registered Authors: Appelbaum, Lior, Elbaz, Idan, Lerer-Goldshtein, Tali, Yelin-Bekerman, Laura
Keywords: hypocretin, kcnh4a, neuroscience, orexin, sleep, transcriptome, zebrafish
MeSH Terms:
  • Animals
  • Gene Expression Profiling*
  • Gene Knockdown Techniques
  • Molecular Sequence Data
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Neurons/physiology*
  • Orexins/genetics
  • Orexins/metabolism*
  • Potassium Channels, Voltage-Gated/genetics
  • Potassium Channels, Voltage-Gated/metabolism*
  • Sequence Analysis, DNA
  • Sleep*
  • Zebrafish/physiology*
PubMed: 26426478 Full text @ Elife
Sleep has been conserved throughout evolution; however, the molecular and neuronal mechanisms of sleep are largely unknown. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate sleep/wake states, feeding, stress, and reward. To elucidate the mechanism that enables these various functions and to identify sleep regulators, we combined fluorescence cell sorting and RNA-seq in hcrt:EGFP zebrafish. Dozens of Hcrt-neuron-specific transcripts were identified and comprehensive high-resolution imaging revealed gene-specific localization in all or subsets of Hcrt neurons. Clusters of Hcrt-neuron-specific genes are predicted to be regulated by shared transcription factors. These findings show that Hcrt neurons are heterogeneous and that integrative molecular mechanisms orchestrate their diverse functions. The voltage-gated potassium channel Kcnh4a, which is expressed in all Hcrt neurons, was silenced by the CRISPR-mediated gene inactivation system. The mutant kcnh4a(kcnh4a-/-) larvae showed reduced sleep time and consolidation, specifically during the night, suggesting that Kcnh4a regulates sleep.