Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, China.
Laboratory Animal Center, Academy of Military Medical Sciences, Beijing, China.
Science. 2023 Jun 2;380(6648):972-979. doi: 10.1126/science.abm1962. Epub 2023 Jun 1.
The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length. Genetic ablation of ciliogenesis in NMS neurons enabled a rapid phase shift of the internal clock under jet-lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lost their coherence after external perturbations. Rhythmic cilia changes drive oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression. Inactivation of Shh signaling in NMS neurons phenocopied the effects of cilia ablation. Thus, cilia-Shh signaling in the SCN aids intercellular coupling.
视交叉上核(SCN)通过细胞间耦合驱动生物钟的同步,这种耦合能抵抗环境干扰。我们报告称,初级纤毛是 SCN 神经元之间细胞间耦合所必需的,以维持小鼠内部时钟的稳健性。神经肽 S 产生(NMS)神经元中的纤毛在丰度和长度上表现出明显的昼夜节律性。NMS 神经元中的纤毛发生基因缺失使内部时钟在倒班条件下能够快速相位移动。纤毛缺陷的 SCN 切片中单个神经元的昼夜节律失去了同步性,这表明细胞间通讯发生了紊乱。纤毛的周期性变化驱动了 Sonic Hedgehog(Shh)信号和时钟基因表达的振荡。NMS 神经元中 Shh 信号的失活模拟了纤毛缺失的影响。因此,SCN 中的纤毛-Shh 信号有助于细胞间耦合。