Laboratorio de Genética del Comportamiento, Fundación Instituto Leloir, IIB-BA-CONICET, Buenos Aires, Argentina.
PLoS Biol. 2013 Dec;11(12):e1001733. doi: 10.1371/journal.pbio.1001733. Epub 2013 Dec 10.
Living organisms use biological clocks to maintain their internal temporal order and anticipate daily environmental changes. In Drosophila, circadian regulation of locomotor behavior is controlled by ∼150 neurons; among them, neurons expressing the PIGMENT DISPERSING FACTOR (PDF) set the period of locomotor behavior under free-running conditions. To date, it remains unclear how individual circadian clusters integrate their activity to assemble a distinctive behavioral output. Here we show that the BONE MORPHOGENETIC PROTEIN (BMP) signaling pathway plays a crucial role in setting the circadian period in PDF neurons in the adult brain. Acute deregulation of BMP signaling causes period lengthening through regulation of dClock transcription, providing evidence for a novel function of this pathway in the adult brain. We propose that coherence in the circadian network arises from integration in PDF neurons of both the pace of the cell-autonomous molecular clock and information derived from circadian-relevant neurons through release of BMP ligands.
生物利用生物钟来维持内部的时间秩序,并预测日常环境变化。在果蝇中,运动行为的昼夜节律调节由约 150 个神经元控制;其中,表达 PIGMENT DISPERSING FACTOR(PDF)的神经元在自由运行条件下设定运动行为的周期。迄今为止,尚不清楚单个昼夜节律簇如何整合其活动以组装独特的行为输出。在这里,我们表明 BONE MORPHOGENETIC PROTEIN(BMP)信号通路在成年大脑中 PDF 神经元的昼夜节律周期设定中起着关键作用。BMP 信号的急性失调通过调节 dClock 转录导致周期延长,为该途径在成年大脑中的新功能提供了证据。我们提出,昼夜节律网络的一致性源于通过释放 BMP 配体从昼夜节律相关神经元中整合细胞自主分子钟的节奏和信息,从而在 PDF 神经元中整合。