Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States.
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States.
Elife. 2020 Mar 23;9:e52676. doi: 10.7554/eLife.52676.
Across species, sleep in young animals is critical for normal brain maturation. The molecular determinants of early life sleep remain unknown. Through an RNAi-based screen, we identified a gene, , required for sleep maturation in , a transcription factor, coordinates an early developmental program that prepares the brain to later execute high levels of juvenile adult sleep. PDM3 controls the wiring of wake-promoting dopaminergic (DA) neurites to a sleep-promoting region, and loss of PDM3 prematurely increases DA inhibition of the sleep center, abolishing the juvenile sleep state. RNA-Seq/ChIP-Seq and a subsequent modifier screen reveal that represses expression of the synaptogenesis gene to establish the appropriate window for DA innervation. These studies define the molecular cues governing sleep behavioral and circuit development, and suggest sleep disorders may be of neurodevelopmental origin.
在不同物种中，幼年动物的睡眠对于正常的大脑成熟至关重要。然而，生命早期睡眠的分子决定因素仍然未知。通过基于 RNAi 的筛选，我们鉴定出一个基因 ，对于 的睡眠成熟是必需的，它是一个转录因子，协调一个早期发育程序，使大脑为以后执行高水平的青少年成人睡眠做好准备。PDM3 控制觉醒促进多巴胺能 (DA) 神经突向睡眠促进区域的布线，而 PDM3 的缺失会过早增加 DA 对睡眠中心的抑制作用，从而消除青少年的睡眠状态。RNA-Seq/ChIP-Seq 和随后的修饰筛选揭示， 抑制突触发生基因 的表达，以建立适当的 DA 支配窗口。这些研究定义了控制睡眠行为和回路发育的分子线索，并表明睡眠障碍可能具有神经发育起源。
