Affiliation:
1. Neuroscience Institute, Department of Neuroscience and Physiology, New York University School of Medicine
2. Waksman Institute, Rutgers University
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 (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.
Funder
Howard Hughes Medical Institute
National Institute of Neurological Disorders and Stroke
G. Harold and Leila Y. Mathers Foundation
Whitehall Foundation
Alfred P. Sloan Foundation
Leon Levy Foundation
Brain and Behavior Research Foundation
Sleep Research Society Foundation
Irma T. Hirschl Trust
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Cited by
5 articles.
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