Wani Adil R, Chowdhury Budhaditya, Luong Jenny, Chaya Gonzalo Morales, Patel Krishna, Isaacman-Beck Jesse, Shafer Orie, Kayser Matthew S, Syed Mubarak Hussain
Neural Diversity Lab, Department of Biology, University of New Mexico, 219 Yale Blvd Ne, 87131 Albuquerque, NM, USA.
The Advanced Science Research Center, City University of New York, New York, NY 10031, USA.
bioRxiv. 2023 Oct 2:2023.09.29.560022. doi: 10.1101/2023.09.29.560022.
Complex behaviors arise from neural circuits that are assembled from diverse cell types. Sleep is a conserved and essential behavior, yet little is known regarding how the nervous system generates neuron types of the sleep-wake circuit. Here, we focus on the specification of sleep-promoting neurons-long-field tangential input neurons that project to the dorsal layers of the fan-shaped body neuropil in the central complex (CX). We use lineage analysis and genetic birth dating to identify two bilateral Type II neural stem cells that generate these dorsal fan-shaped body (dFB) neurons. We show that adult dFB neurons express Ecdysone-induced protein E93, and loss of Ecdysone signaling or E93 in Type II NSCs results in the misspecification of the adult dFB neurons. Finally, we show that E93 knockdown in Type II NSCs affects adult sleep behavior. Our results provide insight into how extrinsic hormonal signaling acts on NSCs to generate neuronal diversity required for adult sleep behavior. These findings suggest that some adult sleep disorders might derive from defects in stem cell-specific temporal neurodevelopmental programs.
复杂行为源于由多种细胞类型组装而成的神经回路。睡眠是一种保守且必不可少的行为,但对于神经系统如何产生睡眠 - 觉醒回路的神经元类型却知之甚少。在这里,我们聚焦于促进睡眠的神经元——长场切向输入神经元的特化,这些神经元投射到中央复合体(CX)中扇形身体神经纤维网的背侧层。我们使用谱系分析和遗传出生时间测定来识别产生这些背侧扇形身体(dFB)神经元的两个双侧II型神经干细胞。我们发现成年dFB神经元表达蜕皮激素诱导蛋白E93,并且II型神经干细胞中蜕皮激素信号或E93的缺失会导致成年dFB神经元的特化错误。最后,我们表明II型神经干细胞中E93的敲低会影响成年睡眠行为。我们的结果为外在激素信号如何作用于神经干细胞以产生成年睡眠行为所需的神经元多样性提供了见解。这些发现表明,一些成人睡眠障碍可能源于干细胞特异性时间神经发育程序的缺陷。