insomniac links the development and function of a sleep-regulatory circuit
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 los...
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Published in | eLife Vol. 10 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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eLife Sciences Publications Ltd
15.12.2021
eLife Sciences Publications, Ltd |
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Abstract | 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. |
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AbstractList | 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. 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. 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. |
Author | Lim, Kayla Y Stavropoulos, Nicholas Li, Qiuling Jang, Hyunsoo Lessing, Alexie |
Author_xml | – sequence: 1 givenname: Qiuling orcidid: 0000-0002-6101-8779 surname: Li fullname: Li, Qiuling organization: Neuroscience Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, United States – sequence: 2 givenname: Hyunsoo orcidid: 0000-0001-9191-3697 surname: Jang fullname: Jang, Hyunsoo organization: Neuroscience Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, United States – sequence: 3 givenname: Kayla Y orcidid: 0000-0001-7168-5877 surname: Lim fullname: Lim, Kayla Y organization: Neuroscience Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, United States – sequence: 4 givenname: Alexie orcidid: 0000-0003-2044-7822 surname: Lessing fullname: Lessing, Alexie organization: Neuroscience Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, United States – sequence: 5 givenname: Nicholas orcidid: 0000-0001-5915-2760 surname: Stavropoulos fullname: Stavropoulos, Nicholas organization: Waksman Institute, Rutgers University, Piscataway, United States |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34908527$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1073_pnas_2312664121 crossref_primary_10_1371_journal_pgen_1010289 crossref_primary_10_1016_j_isci_2024_109634 crossref_primary_10_3389_fphys_2023_1091248 crossref_primary_10_1038_s41598_024_51657_9 |
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Copyright | 2021, Li et al. 2021, Li et al. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2021, Li et al 2021 Li et al |
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Keywords | neuroblast sleep disorders developmental biology neuroscience neurogenesis Cul3 D. melanogaster neurodevelopmental disorders autism |
Language | English |
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Score | 2.3917491 |
Snippet | Although many genes are known to influence sleep, when and how they impact sleep-regulatory circuits remain ill-defined. Here, we show that
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), a conserved... 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 ),... 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... |
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SubjectTerms | 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 |
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Title | insomniac links the development and function of a sleep-regulatory circuit |
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