Neuropeptidergic circuit modulation of developmental sleep in Drosophila

Sleep-wakefulness regulation dynamically evolves along development in flies, fish, and humans. While the mechanisms regulating sleep in adults are relatively well understood, little is known about their counterparts 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 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 Drosophila insulin-like peptides (Dilps) to regulate sleep. We further show that the Hugin/PK2-R1 axis is dispensable for adult sleep control. Our findings thus reveal the neuromodulatory circuitry regulating larval sleep, highlighting differential impacts of the same modulatory axis on developmental sleep and adult sleep.