insomniac links the development and function of a sleep-regulatory circuit

• Published in: eLife Vol. 10
• Main Authors: Li, Qiuling, Jang, Hyunsoo, Lim, Kayla Y, Lessing, Alexie, Stavropoulos, Nicholas
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 15.12.2021; eLife Sciences Publications, Ltd
• Subjects: Acids; Animals; Associative learning; Autism; Brain; Cul3; Developmental Biology; Drosophila melanogaster - genetics; Drosophila melanogaster - physiology; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Influence; Ligands; Mammals; Models, Animal; Mushroom bodies; Mushroom Bodies - physiology; Mutation; neuroblast; Neurodevelopmental disorders; Neurogenesis; Neuroscience; Sensory integration; Sleep; Sleep - genetics; Sleep disorders; Structure-function relationships; Ubiquitin; Ubiquitin-protein ligase; Variance analysis; neuroblast; sleep disorders; developmental biology; neuroscience; neurogenesis; Cul3; D. melanogaster; neurodevelopmental disorders; autism
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.65437

Although many genes are known to influence sleep, when and how they impact sleep-regulatory circuits remain ill-defined. Here, we show that ( ), a conserved adaptor for the autism-associated Cul3 ubiquitin ligase, acts in a restricted period of neuronal development to impact sleep in adult . The loss of causes structural and functional alterations within the mushroom body (MB), a center for sensory integration, associative learning, and sleep regulation. In 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.