TY - JOUR T1 - Rhythmic Cilium in SCN Neuron is a Gatekeeper for the Intrinsic Circadian Clock JF - bioRxiv DO - 10.1101/2022.01.26.477948 SP - 2022.01.26.477948 AU - Hai-Qing Tu AU - Sen Li AU - Yu-Ling Xu AU - Yu-Cheng Zhang AU - Xiao-Xiao Jian AU - Guang-Ping Song AU - Min Wu AU - Zeng-Qing Song AU - Huai-Bin Hu AU - Pei-Yao Li AU - Li-Yun Liang AU - Jin-Feng Yuan AU - Xiao-Lin Shen AU - Jia-Ning Li AU - Qiu-Ying Han AU - Kai Wang AU - Tao Zhang AU - Tao Zhou AU - Ai-Ling Li AU - Xue-Min Zhang AU - Hui-Yan Li Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/02/01/2022.01.26.477948.abstract N2 - The internal circadian rhythm is controlled by the central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN). SCN drives coherent and synchronized circadian oscillations via intercellular coupling, which are resistant to environmental perturbations. Here we report that primary cilium is a critical device for intercellular coupling among SCN neurons and acts as a gatekeeper to maintain the internal clock in mice. A subset of SCN neurons, namely neuromedin S-producing (NMS) neurons, exhibit cilia dynamics with a pronounced circadian rhythmicity. Genetic ablation of ciliogenesis in NMS neurons enables a rapid phase shift of the internal clock under experimental jet lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lose their coherence following external perturbations. Rhythmic cilia dynamics drive oscillations of Sonic Hedgehog (Shh) signaling and oscillated expressions of multiple circadian genes in SCN neurons. Genetic and chemical inactivation of Shh signaling in NMS neurons phenocopies the effect of cilia ablation. Our findings establish ciliary signaling as a novel interneuronal coupling mechanism in the SCN and may lead to novel therapy of circadian disruption-linked diseases.One-Sentence Summary Rhythmic cilium is a critical device for intercellular coupling among SCN neurons and acts as gatekeeper for the internal clock.Competing Interest StatementThe authors have declared no competing interest. ER -