Retrograde bone morphogenetic protein signaling shapes a key circadian pacemaker circuit.
Retrograde bone morphogenetic protein signaling shapes a key circadian pacemaker circuit.
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DOI：
10.1523/jneurosci.3448-12.2013
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发表时间：
2013-01-09
期刊：
影响因子：
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通讯作者：
Ceriani MF
中科院分区：
文献类型：
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作者：
Gorostiza EA;Ceriani MF
神经肽色素分散因子（PDF）抑制果蝇脑中昼夜节律起搏器内的分子振荡。它在小的腹侧神经元（sLNvs）和大的腹侧神经元中表达，前者对于在自由奔跑条件下维持行为节律性是不可或缺的。PDF回路如何发展出赋予这种全局行为控制的特定连接特性，目前尚不清楚。在这里，我们表明，成熟的sLNv电路需要PDF信号在早期发展过程中，通过其同源受体PDFR在突触后的目标。然而，轴突缺陷的PDF敲低突触前，并成为明显的变态后，突出了延迟响应的信号释放早on.Presynaptic表达的组成型活性骨形态发生蛋白（BMP）受体防止pdfr突变体路由错误的表型，而sLNV限制性下调BMP信号传导组件phenocopied pdf 01。因此，我们已经发现了一种新的机制，提供了一个早期的“标签”的突触目标，将指导电路完善以后的发展。
The neuropeptide pigment-dispersing factor (PDF) synchronizes molecular oscillations within circadian pacemakers in the Drosophila brain. It is expressed in the small ventral lateral neurons (sLNvs) and large ventral lateral neurons, the former being indispensable for maintaining behavioral rhythmicity under free-running conditions. How PDF circuits develop the specific connectivity traits that endow such global behavioral control remains unknown. Here, we show that mature sLNv circuits require PDF signaling during early development, acting through its cognate receptor PDFR at postsynaptic targets. Yet, axonal defects by PDF knockdown are presynaptic and become apparent only after metamorphosis, highlighting a delayed response to a signal released early on. Presynaptic expression of constitutively active bone morphogenetic protein (BMP) receptors prevents pdfr mutants misrouting phenotype, while sLNv-restricted downregulation of BMP signaling components phenocopied pdf01. Thus, we have uncovered a novel mechanism that provides an early “tagging” of synaptic targets that will guide circuit refinement later in development.