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The chromatin remodeler ISWI acts during Drosophila development to regulate adult sleep

Sleep disruptions are among the most commonly reported symptoms across neurodevelopmental disorders (NDDs), but mechanisms linking brain development to normal sleep are largely unknown. From a Drosophila screen of human NDD-associated risk genes, we identified the chromatin remodeler Imitation SWItc...

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Autores principales: Gong, Naihua N., Dilley, Leela Chakravarti, Williams, Charlette E., Moscato, Emilia H., Szuperak, Milan, Wang, Qin, Jensen, Matthew, Girirajan, Santhosh, Tan, Tiong Yang, Deardorff, Matthew A., Li, Dong, Song, Yuanquan, Kayser, Matthew S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888929/
https://www.ncbi.nlm.nih.gov/pubmed/33597246
http://dx.doi.org/10.1126/sciadv.abe2597
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author Gong, Naihua N.
Dilley, Leela Chakravarti
Williams, Charlette E.
Moscato, Emilia H.
Szuperak, Milan
Wang, Qin
Jensen, Matthew
Girirajan, Santhosh
Tan, Tiong Yang
Deardorff, Matthew A.
Li, Dong
Song, Yuanquan
Kayser, Matthew S.
author_facet Gong, Naihua N.
Dilley, Leela Chakravarti
Williams, Charlette E.
Moscato, Emilia H.
Szuperak, Milan
Wang, Qin
Jensen, Matthew
Girirajan, Santhosh
Tan, Tiong Yang
Deardorff, Matthew A.
Li, Dong
Song, Yuanquan
Kayser, Matthew S.
author_sort Gong, Naihua N.
collection PubMed
description Sleep disruptions are among the most commonly reported symptoms across neurodevelopmental disorders (NDDs), but mechanisms linking brain development to normal sleep are largely unknown. From a Drosophila screen of human NDD-associated risk genes, we identified the chromatin remodeler Imitation SWItch/SNF (ISWI) to be required for adult fly sleep. Loss of ISWI also results in disrupted circadian rhythms, memory, and social behavior, but ISWI acts in different cells and during distinct developmental times to affect each of these adult behaviors. Specifically, ISWI expression in type I neuroblasts is required for both adult sleep and formation of a learning-associated brain region. Expression in flies of the human ISWI homologs SMARCA1 and SMARCA5 differentially rescues adult phenotypes, while de novo SMARCA5 patient variants fail to rescue sleep. We propose that sleep deficits are a primary phenotype of early developmental origin in NDDs and point toward chromatin remodeling machinery as critical for sleep circuit formation.
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spelling pubmed-78889292021-02-24 The chromatin remodeler ISWI acts during Drosophila development to regulate adult sleep Gong, Naihua N. Dilley, Leela Chakravarti Williams, Charlette E. Moscato, Emilia H. Szuperak, Milan Wang, Qin Jensen, Matthew Girirajan, Santhosh Tan, Tiong Yang Deardorff, Matthew A. Li, Dong Song, Yuanquan Kayser, Matthew S. Sci Adv Research Articles Sleep disruptions are among the most commonly reported symptoms across neurodevelopmental disorders (NDDs), but mechanisms linking brain development to normal sleep are largely unknown. From a Drosophila screen of human NDD-associated risk genes, we identified the chromatin remodeler Imitation SWItch/SNF (ISWI) to be required for adult fly sleep. Loss of ISWI also results in disrupted circadian rhythms, memory, and social behavior, but ISWI acts in different cells and during distinct developmental times to affect each of these adult behaviors. Specifically, ISWI expression in type I neuroblasts is required for both adult sleep and formation of a learning-associated brain region. Expression in flies of the human ISWI homologs SMARCA1 and SMARCA5 differentially rescues adult phenotypes, while de novo SMARCA5 patient variants fail to rescue sleep. We propose that sleep deficits are a primary phenotype of early developmental origin in NDDs and point toward chromatin remodeling machinery as critical for sleep circuit formation. American Association for the Advancement of Science 2021-02-17 /pmc/articles/PMC7888929/ /pubmed/33597246 http://dx.doi.org/10.1126/sciadv.abe2597 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Gong, Naihua N.
Dilley, Leela Chakravarti
Williams, Charlette E.
Moscato, Emilia H.
Szuperak, Milan
Wang, Qin
Jensen, Matthew
Girirajan, Santhosh
Tan, Tiong Yang
Deardorff, Matthew A.
Li, Dong
Song, Yuanquan
Kayser, Matthew S.
The chromatin remodeler ISWI acts during Drosophila development to regulate adult sleep
title The chromatin remodeler ISWI acts during Drosophila development to regulate adult sleep
title_full The chromatin remodeler ISWI acts during Drosophila development to regulate adult sleep
title_fullStr The chromatin remodeler ISWI acts during Drosophila development to regulate adult sleep
title_full_unstemmed The chromatin remodeler ISWI acts during Drosophila development to regulate adult sleep
title_short The chromatin remodeler ISWI acts during Drosophila development to regulate adult sleep
title_sort chromatin remodeler iswi acts during drosophila development to regulate adult sleep
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888929/
https://www.ncbi.nlm.nih.gov/pubmed/33597246
http://dx.doi.org/10.1126/sciadv.abe2597
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