Rhythmic cilia changes support SCN neuron coherence in circadian clock

Science. 2023 Jun 2;380(6648):972-979. doi: 10.1126/science.abm1962. Epub 2023 Jun 1.

Abstract

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.

MeSH terms

  • Animals
  • Cilia* / metabolism
  • Cilia* / physiology
  • Circadian Clocks* / genetics
  • Circadian Rhythm* / physiology
  • Gene Expression Regulation
  • Hedgehog Proteins* / genetics
  • Hedgehog Proteins* / metabolism
  • Mice
  • Mice, Transgenic
  • Signal Transduction
  • Suprachiasmatic Nucleus Neurons* / physiology

Substances

  • Hedgehog Proteins