4.8 Article

Rhythmic cilia changes support SCN neuron coherence in circadian clock

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SCIENCE
卷 380, 期 6648, 页码 972-979

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abm1962

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The primary cilia in neuromedin S-producing (NMS) neurons are crucial for intercellular coupling and maintaining the robustness of the internal clock in the suprachiasmatic nucleus (SCN) of mice. Genetic ablation of ciliogenesis in NMS neurons leads to rapid phase shifts of the internal clock under jet-lag conditions and loss of coherence in the circadian rhythms of individual neurons. The cilia-Shh signaling pathway plays a role in intercellular coupling by driving oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression.
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.

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