TY - JOUR TI - insomniac links the development and function of a sleep-regulatory circuit AU - Li, Qiuling AU - Jang, Hyunsoo AU - Lim, Kayla Y AU - Lessing, Alexie AU - Stavropoulos, Nicholas A2 - Calabrese, Ronald L A2 - Cirelli, Chiara VL - 10 PY - 2021 DA - 2021/12/15 SP - e65437 C1 - eLife 2021;10:e65437 DO - 10.7554/eLife.65437 UR - https://doi.org/10.7554/eLife.65437 AB - Although many genes are known to influence sleep, when and how they impact sleep-regulatory circuits remain ill-defined. Here, we show that insomniac (inc), a conserved adaptor for the autism-associated Cul3 ubiquitin ligase, acts in a restricted period of neuronal development to impact sleep in adult Drosophila. The loss of inc causes structural and functional alterations within the mushroom body (MB), a center for sensory integration, associative learning, and sleep regulation. In inc mutants, MB neurons are produced in excess, develop anatomical defects that impede circuit assembly, and are unable to promote sleep when activated in adulthood. Our findings link neurogenesis and postmitotic development of sleep-regulatory neurons to their adult function and suggest that developmental perturbations of circuits that couple sensory inputs and sleep may underlie sleep dysfunction in neurodevelopmental disorders. KW - neurogenesis KW - neuroblast KW - autism KW - neurodevelopmental disorders KW - Cul3 KW - sleep disorders JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -