Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior
Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior
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DOI：
10.1371/journal.pgen.1006445
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发表时间：
2016-11-01
期刊：
影响因子：
4.5
通讯作者：
Gothilf, Yoav
中科院分区：
文献类型：
--
作者：
Livne, Zohar Ben-Moshe;Alon, Shahar;Gothilf, Yoav
人们认为鱼类的主要生物钟位于松果体中。然而，这一教条受到了挑战，因为我们发现大多数斑马鱼组织都含有可直接被光重置的分子钟。为了进一步研究松果体振荡器在斑马鱼昼夜节律系统中的作用，我们产生了一个转基因品系，其中通过显性失活策略选择性地阻断松果体产生褪黑激素的细胞中的分子钟。结果，成人松果体中由时钟控制的褪黑激素产生节律被打乱。此外，转录组分析表明，成年松果体中大多数时钟控制基因的昼夜节律表达模式被废除。重要的是，斑马鱼幼虫的昼夜节律行为受到影响：持续黑暗下的位置偏好节律被消除，持续黑暗和持续昏暗光线条件下的运动活动节律明显减弱。另一方面，在整个幼虫中测量的整体外周分子振荡器在此模型中未受影响。总之，这种新型转基因模型的表征提供了证据，证明松果体产生褪黑激素的细胞中的分子钟在调节行为的昼夜节律中发挥着关键作用，可能作为多起搏器系统的一部分。
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.