PUBLICATION
Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a
- Authors
- Yelin-Bekerman, L., Elbaz, I., Diber, A., Dahary, D., Gibbs-Bar, L., Alon, S., Lerer-Goldshtein, T., Appelbaum, L.
- ID
- ZDB-PUB-151002-1
- Date
- 2015
- Source
- eLIFE 4: e08638 (Journal)
- Registered Authors
- Appelbaum, Lior, Elbaz, Idan, Yelin-Bekerman, Laura
- Keywords
- hypocretin, kcnh4a, neuroscience, orexin, sleep, transcriptome, zebrafish
- MeSH Terms
-
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism*
- Potassium Channels, Voltage-Gated/genetics
- Potassium Channels, Voltage-Gated/metabolism*
- Sleep*
- PubMed
- 26426478 Full text @ Elife
Abstract
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.
Genes / Markers
Figure Gallery (8 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping