title: Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a.
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.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.|The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Laura
authors.initials: L
authors.lastname: Yelin-Bekerman
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.|The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Idan
authors.initials: I
authors.lastname: Elbaz
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.|The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Alex
authors.initials: A
authors.lastname: Diber
authors.affiliation: Toldot Genetics Ltd., Hod Hasharon, Israel.
authors.forename: Dvir
authors.initials: D
authors.lastname: Dahary
authors.affiliation: The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Liron
authors.initials: L
authors.lastname: Gibbs-Bar
authors.affiliation: Media Lab, Massachusetts Institute of Technology, Cambridge, United states.
authors.forename: Shahar
authors.initials: S
authors.lastname: Alon
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.|The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Lerer-Goldshtein
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.|The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Appelbaum
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D000068797:Orexins / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D012890:Sleep; D015027:Zebrafish / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D000068797:Orexins; D024642:Potassium Channels, Voltage-Gated
keywords: hypocretin; kcnh4a; neuroscience; orexin; sleep; transcriptome; zebrafish