Drosophila free-running rhythms require intercellular communication.
Drosophila free-running rhythms require intercellular communication.
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DOI：
10.1371/journal.pbio.0000013
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发表时间：
2003-10
期刊：
影响因子：
9.8
通讯作者：
Rosbash M
中科院分区：
文献类型：
--
作者：
Peng Y;Stoleru D;Levine JD;Hall JC;Rosbash M
强大的自我维持振荡是昼夜节律的普遍特征。其中包括果蝇的运动活动节律，这种节律在持续黑暗（DD）中持续数周。然而，在许多果蝇组织中，昼夜节律背后的分子振荡迅速减弱。尽管在理解昼夜节律的生化和细胞基础方面已经取得了很大进展，但阻尼振荡和自我维持振荡之间差异的机制仍然很大程度上未知。成年果蝇大脑中的一小群神经元，即腹侧外侧神经元（LNvs），对于自我维持的行为节律至关重要，并被认为是运动活动节律的主要起搏器。通过 LNv 特异性驱动器，我们限制了这些神经元的功能时钟，并表明它们不足以驱动昼夜节律运动活动节律。同样与预期相反的是，我们发现所有大脑时钟神经元在 DD 中都表现出持续多天的永恒和隐花 RNA 的强烈昼夜节律振荡。这种持久的分子节律需要色素分散因子（PDF），一种 LNv 特异性神经肽，因为当 Pdf01 突变果蝇暴露于自由奔跑条件时，分子振荡逐渐消失。这一观察结果与之前报道的 Pdf01 突变体行为节律的影响完全相同。 PDF 可能会直接影响一些时钟神经元，因为该肽似乎与许多时钟神经元的表面结合，包括 LNv 本身。我们发现，果蝇的大脑生物钟与眼睛和其他快速阻尼的外周组织有着明显的区别，因为它在 DD 中维持着强大的分子振荡。与此同时，不同的时钟神经元可能在大脑内协同工作，因为单独的 LNv 不足以支持昼夜节律程序。根据 Pdf01 突变果蝇的阻尼结果，我们提出 LNvs，特别是它合成的 PDF 神经肽，对于协调大脑内的昼夜节律细胞网络非常重要。该网络的协作功能似乎对于维持 DD 中强大的分子振荡是必要的，并且是持续昼夜运动活动节律的基础。昼夜节律的特点是强大的分子振荡，此处显示需要大脑区域特定的神经肽 PDF 来维持和协调
Robust self-sustained oscillations are a ubiquitous characteristic of circadian rhythms. These include Drosophila locomotor activity rhythms, which persist for weeks in constant darkness (DD). Yet the molecular oscillations that underlie circadian rhythms damp rapidly in many Drosophila tissues. Although much progress has been made in understanding the biochemical and cellular basis of circadian rhythms, the mechanisms that underlie the differences between damped and self-sustaining oscillations remain largely unknown. A small cluster of neurons in adult Drosophila brain, the ventral lateral neurons (LNvs), is essential for self-sustained behavioral rhythms and has been proposed to be the primary pacemaker for locomotor activity rhythms. With an LNv-specific driver, we restricted functional clocks to these neurons and showed that they are not sufficient to drive circadian locomotor activity rhythms. Also contrary to expectation, we found that all brain clock neurons manifest robust circadian oscillations of timeless and cryptochrome RNA for many days in DD. This persistent molecular rhythm requires pigment-dispersing factor (PDF), an LNv-specific neuropeptide, because the molecular oscillations are gradually lost when Pdf01 mutant flies are exposed to free-running conditions. This observation precisely parallels the previously reported effect on behavioral rhythms of the Pdf01 mutant. PDF is likely to affect some clock neurons directly, since the peptide appears to bind to the surface of many clock neurons, including the LNvs themselves. We showed that the brain circadian clock in Drosophila is clearly distinguishable from the eyes and other rapidly damping peripheral tissues, as it sustains robust molecular oscillations in DD. At the same time, different clock neurons are likely to work cooperatively within the brain, because the LNvs alone are insufficient to support the circadian program. Based on the damping results with Pdf01 mutant flies, we propose that LNvs, and specifically the PDF neuropeptide that it synthesizes, are important in coordinating a circadian cellular network within the brain. The cooperative function of this network appears to be necessary for maintaining robust molecular oscillations in DD and is the basis of sustained circadian locomotor activity rhythms. Circadian rhythms are characterized by robust molecular oscillations, which are shown here to require a brain region-specific neuropeptide, PDF, for maintenance and coordination
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影响因子：
5.3
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64.5
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