title: Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior.
abstract: The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior.
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Zohar
authors.identifier: http://orcid.org/0000-0002-5452-6759
authors.initials: Z
authors.lastname: Ben-Moshe Livne
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.|Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Shahar
authors.initials: S
authors.lastname: Alon
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vallone
authors.affiliation: Unit on Behavioral Neurogenetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Yared
authors.identifier: http://orcid.org/0000-0001-7553-8516
authors.initials: Y
authors.lastname: Bayleyen
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Tovin
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Shainer
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie Intégrative des Organismes Marins, Observatoire Océanologique, Banyuls/Mer, France.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Nisembaum
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Idit
authors.initials: I
authors.lastname: Aviram
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Sima
authors.initials: S
authors.lastname: Smadja-Storz
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie Intégrative des Organismes Marins, Observatoire Océanologique, Banyuls/Mer, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Fuentes
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie Intégrative des Organismes Marins, Observatoire Océanologique, Banyuls/Mer, France.
authors.forename: Jack
authors.initials: J
authors.lastname: Falcón
authors.affiliation: Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.|Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Eisenberg
authors.affiliation: Section on Neuroendocrinology and Office of the Scientific Directory, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Klein
authors.affiliation: Unit on Behavioral Neurogenetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Harold A
authors.initials: HA
authors.lastname: Burgess
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Foulkes
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.|Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gothilf
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003624:Darkness; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008027:Light; D008124:Locomotion / Q000235:genetics* / Q000502:physiology; D008550:Melatonin / Q000096:biosynthesis* / Q000235:genetics; D010870:Pineal Gland / Q000254:growth & development / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins
chemical_list: D004268:DNA-Binding Proteins; D029961:Zebrafish Proteins; C541354:clocka protein, zebrafish; D008550:Melatonin