Neuropeptides PDF and DH31 hierarchically regulate free-running rhythmicity in Drosophila circadian locomotor activity
Neuropeptides PDF and DH31 hierarchically regulate free-running rhythmicity in Drosophila circadian locomotor activity
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DOI：
10.1038/s41598-018-37107-3
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发表时间：
2019-01-29
影响因子：
4.6
通讯作者：
Hamada, Fumika N.
中科院分区：
文献类型：
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作者：
Goda, Tadahiro;Umezaki, Yujiro;Hamada, Fumika N.
神经肽在调节昼夜节律中起着关键作用。色素分散因子（PDF）对果蝇运动活动的昼夜节律至关重要。在这里，我们证明了利尿激素31（DH 31）补充PDF功能，在调节自由运行的节奏，使用雄性苍蝇。我们确定Dh 31功能丧失突变体（Dh 31（#51））显示出正常的节律性，而Dh 31（#51）;Pdf（01）双突变体与Pdf无效突变体（Pdf（01））相比表现出严重的节律表型。栓系PDF或栓系DH 31在时钟细胞后背神经元1（DN 1 ps）中的表达克服了Dh 31（#51）; Pdf（01）双突变体的严重不稳定性，表明DH 31和PDF可能以分级方式作用于DN 1 ps以调节自由运行的节律性。出乎意料的是，Dh 31（#51）; Pdf（01）突变体中的分子振荡与DN 1 ps中Pdf（01）突变体中的分子振荡相似，表明DH 31对分子振荡没有贡献。此外，Dh 31受体（Dh 31 r）表达的减少导致正常的运动活动，并没有增强由Pdf受体（Pdfr）突变引起的运动表型，这表明DN 1 ps中的PDFR而不是DH 31 R主要调节自由运行的节律性。综上所述，我们确定了DH 31的新作用，其中DH 31和PDF通过DN 1 ps分级调节自由运行的节律性。
Neuropeptides play pivotal roles in modulating circadian rhythms. Pigment-dispersing factor (PDF) is critical to the circadian rhythms in Drosophila locomotor activity. Here, we demonstrate that diuretic hormone 31 (DH31) complements PDF function in regulating free-running rhythmicity using male flies. We determined that Dh31 loss-of-function mutants (Dh31(#51)) showed normal rhythmicity, whereas Dh31(#51);Pdf(01) double mutants exhibited a severe arrhythmic phenotype compared to Pdf-null mutants (Pdf(01)). The expression of tethered-PDF or tethered-DH31 in clock cells, posterior dorsal neurons 1 (DN1ps), overcomes the severe arrhythmicity of Dh31(#51); Pdf(01) double mutants, suggesting that DH31 and PDF may act on DN1ps to regulate free-running rhythmicity in a hierarchical manner. Unexpectedly, the molecular oscillations in Dh31(#51); Pdf(01) mutants were similar to those in Pdf(01) mutants in DN1ps, indicating that DH31 does not contribute to molecular oscillations. Furthermore, a reduction in Dh31 receptor (Dh31r) expression resulted in normal locomotor activity and did not enhance the arrhythmic phenotype caused by the Pdf receptor (Pdfr) mutation, suggesting that PDFR, but not DH31R, in DN1ps mainly regulates free-running rhythmicity. Taken together, we identify a novel role of DH31, in which DH31 and PDF hierarchically regulate free-running rhythmicity through DN1ps.