Differential clock comparisons with a multiplexed optical lattice clock

Zheng, Xin; Dolde, Jonathan; Lochab, Varun; Merriman, Brett N.; Li, Haoran; Kolkowitz, Shimon

doi:10.1038/s41586-021-04344-y

Daily behavioral and physiological rhythms are controlled by the brain’s circadian timekeeping system, a synchronized network of neurons that maintains endogenous molecular oscillations. These oscillations are based on transcriptional feedback loops of clock genes, which inDrosophilainclude the transcriptional activatorsClock (Clk)andcycle (cyc). While the mechanisms underlying this molecular clock are very well characterized, the roles that the core clock genes play in neuronal physiology and development are much less understood. TheDrosophilatimekeeping center is composed of ~150 clock neurons, among which the four small ventral lateral neurons (sLN_vs) are the most dominant pacemakers under constant conditions. Here, we show that downregulating the clock genecycspecifically in thePdf-expressing neurons leads to decreased fasciculation both in larval and adult brains. This effect is due to a developmental role ofcyc, as both knocking downcycor expressing a dominant negative form ofcycexclusively during development lead to defasciculation phenotypes in adult clock neurons.Clkdownregulation also leads to developmental effects on sLNv morphology. Our results reveal a non-circadian role forcyc, shedding light on the additional functions of circadian clock genes in the development of the nervous system.

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