The proper wiring of neuronal circuits during development is essential for the neuronal control of behavior. Across animal species, sleep/wake cycle rhythms, as well as many other behavioral and physiological rhythms, are controlled by the circadian timekeeping system, a network of neurons that maintains endogenous molecular oscillations and rhythmic behavior with a ~24 hour period. The proper functioning of this circadian network requires the formation of synaptic and peptidergic connections during development.
We recently showed that the circadian clock cycle (cyc), beyond its function in maintaining circadian rhythms, also influences the development of key clock neurons. Specifically, reducing cyc expression in a group of clock neurons during development leads to defects in the morphology of those neurons in both larval and adult stages and affects the ability of adult flies to maintain behavioral rhythms in the absence of environmental cues. These findings reveal that clock genes like cyc have important roles in brain development, highlighting their broader significance beyond circadian regulation.
Cyc is a homolog of the mammalian gene Bmal1, and there is growing evidence for non-circadian functions of BMAL1: it regulates apoptosis and cell-cycle in models of glioblastoma, and Bmal1(-/-) mice exhibit defects in short- and long-term memory formation, reduced lifespan and multiple symptoms of premature aging. Overall, results from studies in different animal models suggest that Bmal1 plays a role in the development of various neurological disorders. We are currently studying the 'non circadian' roles of cannonical clock genes such as cyc to understand their contributions to neuronal development and physiology