TheDrosophilaCircadian Clock GeneCycleControls Development of Clock Neurons

Abstract

AbstractDaily 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 (sLNvs) are the most dominant pacemakers under constant conditions. The sLNvs express the neuropeptide Pigment Dispersing Factor (PDF), a key output signal within the clock neuron network. Here, we show that downregulating the clock genecycspecifically in thePdf-expressing neurons prevents the formation of axonal bundles within which projections normally navigate toward the dorsal brain. This effect is due to a developmental role ofcyc, as both knockdowncycor expressing a dominant negative form ofcycexclusively during development lead to phenotypes in adult clock neurons. Expressing a dominant negativeClkalso leads to developmental effects on sLNv morphology, butcycandclkmanipulations produce distinct phenotypes. Our results reveal a non-circadian role forcyc, shedding light on additional functions of circadian clock genes in the development of the nervous system.