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

Naihua N. Gong, Leela Chakravarti Dilley, Charlette E. Williams, Emilia H. Moscato, Milan Szuperak, Qin Wang, Matthew Jensen, Santhosh Girirajan, Tiong Yang Tan, Matthew A. Deardorff, Dong Li, Yuanquan Song, Matthew S. Kayser

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Article numbereabe2597
JournalScience Advances
Issue number8
StatePublished - Feb 17 2021

All Science Journal Classification (ASJC) codes

  • General


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