insomniac links the development and function of a sleep regulatory circuit
- New York University School of Medicine, United States
Abstract
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, a center for sensory integration, associative learning, and sleep regulation. In inc mutants, mushroom body 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.
Data availability
Data for all figures and code used to analyze sleep are included in the supporting files.
Article and author information
Author details
Nicholas Stavropoulos
Funding
Howard Hughes Medical Institute (International Student Research Fellowship)
- Qiuling Li
Irma T. Hirschl Trust (Career Scientist Award)
- Nicholas Stavropoulos
National Institute of Neurological Disorders and Stroke (R01NS112844)
- Nicholas Stavropoulos
National Institute of Neurological Disorders and Stroke (R21NS111304)
- Nicholas Stavropoulos
G. Harold and Leila Y. Mathers Foundation
- Nicholas Stavropoulos
Whitehall Foundation (2013-05-78)
- Nicholas Stavropoulos
Alfred P. Sloan Foundation
- Nicholas Stavropoulos
Leon Levy Foundation
- Nicholas Stavropoulos
Brain and Behavior Research Foundation (NARSAD Young Investigator)
- Nicholas Stavropoulos
Sleep Research Society Foundation (J. Christian Gillin,M.D. Research Award)
- Nicholas Stavropoulos
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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insomniac links the development and function of a sleep regulatory circuit
eLife 10:e65437.
https://doi.org/10.7554/eLife.65437
