Neuropeptidergic circuit modulation of developmental sleep in Drosophila

Sleep-wakefulness regulation dynamically evolves along development in a wide range of organisms. While the mechanism regulating sleep in adults is relatively well understood, little is known about its counterpart in early developmental stages. Here, we report a neuropeptidergic circuitry that modulates sleep in developing Drosophila larvae. Through an unbiased screen, we identified the neuropeptide Hugin and its receptor PK2-R1 as critical regulators of larval sleep. Our genetic and behavioral data suggest that HugPC neurons secrete Hugin peptides to activate insulin-producing cells (IPCs), which express a Hugin receptor PK2-R1. IPCs, in turn, release insulin-like peptides (Dilps) to regulate sleep. We further show that the Hugin/PK2-R1 axis is dispensable for adult sleep. Our findings thus reveal the neuromodulatory circuit that regulates developmental sleep in larvae and highlight differential impacts of the same modulatory axis on early-life sleep and adult sleep.