Neural Diversity Lab, Department of Biology, University of New Mexico, 219 Yale Blvd Ne, Albuquerque, NM 87131, USA.
The Advanced Science Research Center, City University of New York, New York, NY 10031, USA.
Curr Biol. 2024 Nov 4;34(21):4951-4967.e5. doi: 10.1016/j.cub.2024.09.020. Epub 2024 Oct 8.
Complex behaviors arise from neural circuits that assemble from diverse cell types. Sleep is a conserved behavior essential for survival, yet little is known about how the nervous system generates neuron types of a sleep-wake circuit. Here, we focus on the specification of Drosophila 23E10-labeled dorsal fan-shaped body (dFB) long-field tangential input neurons that project to the dorsal layers of the fan-shaped body neuropil in the central complex. We use lineage analysis and genetic birth dating to identify two bilateral type II neural stem cells (NSCs) that generate 23E10 dFB neurons. We show that adult 23E10 dFB neurons express ecdysone-induced protein 93 (E93) and that loss of ecdysone signaling or E93 in type II NSCs results in their misspecification. Finally, we show that E93 knockdown in type II NSCs impairs adult sleep behavior. Our results provide insight into how extrinsic hormonal signaling acts on NSCs to generate the 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.
复杂的行为源于组装自多种细胞类型的神经回路。睡眠是一种保守的生存行为，但人们对神经系统如何产生睡眠-觉醒回路的神经元类型知之甚少。在这里，我们专注于鉴定果蝇 23E10 标记的背扇形体（dFB）长场切向输入神经元，这些神经元投射到中央复合体中扇形体神经丛的背层。我们使用谱系分析和遗传出生标记来鉴定产生 23E10 dFB 神经元的两个双侧 II 型神经干细胞（NSC）。我们表明，成年 23E10 dFB 神经元表达蜕皮激素诱导蛋白 93（E93），并且在 II 型 NSCs 中缺失蜕皮激素信号或 E93 会导致它们的错误指定。最后，我们表明，在 II 型 NSCs 中敲低 E93 会损害成年睡眠行为。我们的研究结果提供了有关外源性激素信号如何作用于 NSCs 以产生成年睡眠行为所需的神经元多样性的见解。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空神经发育程序的缺陷。
