Systematic modeling-driven experiments identify distinct molecular clockworks underlying hierarchically organized pacemaker neurons

How the circadian clock can be simultaneously robust and flexible

30 June 2022

The molecular mechanisms that enable the circadian clock to be both strong and flexible have been uncovered for the first time.

From flies to people, animals have circadian clocks that keep their body processes roughly in sync with the 24-hour day–night cycle. The neurons responsible for this are organized hierarchically, with master clock neurons receiving signals from the environment and slave clock neurons regulating body processes such as sleep and digestion.

Now, in a finding that goes against conventional wisdom, a team led by researchers from the Institute for Basic Science in South Korea has shown that master and slave clock neurons have distinct molecular mechanisms.

Experiments with fruit flies showed that master clock neurons create and degrade a circadian repressor protein called PER at higher rates than slave clock neurons and that they have lower activator levels.

Computer modelling revealed that this arrangement enabled master clock neurons to generate strong but flexible rhythms.

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References

1. PNAS 119, e2113403119 (2022). doi: 10.1073/pnas.2113403119