Kucherenko Mariya M, Ilangovan Vinodh, Herzig Bettina, Shcherbata Halyna R, Bringmann Henrik
Max Planck Research Group Gene Expression and Signaling, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077, Göttingen, Germany.
Department of Genes and Behavior, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
BMC Neurosci. 2016 Nov 9;17(1):72. doi: 10.1186/s12868-016-0306-3.
The AP-2 transcription factor APTF-1 is crucially required for developmentally controlled sleep behavior in Caenorhabditis elegans larvae. Its human ortholog, TFAP-2beta, causes Char disease and has also been linked to sleep disorders. These data suggest that AP-2 transcription factors may be highly conserved regulators of various types of sleep behavior. Here, we tested the idea that AP-2 controls adult sleep in Drosophila.
Drosophila has one AP-2 ortholog called TfAP-2, which is essential for viability. To investigate its potential role in sleep behavior and neural development, we specifically downregulated TfAP-2 in the nervous system. We found that neuronal TfAP-2 knockdown almost completely abolished night sleep but did not affect day sleep. TfAP-2 insufficiency affected nervous system development. Conditional TfAP-2 knockdown in the adult also produced a modest sleep phenotype, suggesting that TfAP-2 acts both in larval as well as in differentiated neurons.
Thus, our results show that AP-2 transcription factors are highly conserved regulators of development and sleep.
转录因子APTF-1对于秀丽隐杆线虫幼虫发育过程中受调控的睡眠行为至关重要。其人类同源物TFAP-2β会导致Char病,并且也与睡眠障碍有关。这些数据表明,AP-2转录因子可能是各类睡眠行为的高度保守的调节因子。在此,我们测试了AP-2控制果蝇成虫睡眠这一想法。
果蝇有一个名为TfAP-2的AP-2同源物,它对于果蝇的生存能力至关重要。为了研究其在睡眠行为和神经发育中的潜在作用,我们在神经系统中特异性下调了TfAP-2。我们发现,神经元中TfAP-2的敲低几乎完全消除了夜间睡眠,但不影响白天睡眠。TfAP-2功能不足影响了神经系统的发育。在成虫中条件性敲低TfAP-2也产生了适度的睡眠表型,这表明TfAP-2在幼虫以及分化的神经元中均发挥作用。
因此,我们的结果表明,AP-2转录因子是发育和睡眠的高度保守的调节因子。