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Dis Model Mech. 2019 Mar 25;12(3). pii: dmm037325. doi: 10.1242/dmm.037325.

Individual components of the SWI/SNF chromatin remodelling complex have distinct roles in memory neurons of the Drosophila mushroom body.

Author information

1
Department of Biology, Faculty of Science, Western University, London, ON N6A 5B7, Canada.
2
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
3
Division of Genetics and Development, Children's Health Research Institute, London, ON N6C 2V5, Canada.
4
Department of Biology, Faculty of Science, Western University, London, ON N6A 5B7, Canada James.Kramer@schulich.uwo.ca.

Abstract

Technology has led to rapid progress in the identification of genes involved in neurodevelopmental disorders such as intellectual disability (ID), but our functional understanding of the causative genes is lagging. Here, we show that the SWI/SNF chromatin remodelling complex is one of the most over-represented cellular components disrupted in ID. We investigated the role of individual subunits of this large protein complex using targeted RNA interference in post-mitotic memory-forming neurons of the Drosophila mushroom body (MB). Knockdown flies were tested for defects in MB morphology, short-term memory and long-term memory. Using this approach, we identified distinct roles for individual subunits of the Drosophila SWI/SNF complex. Bap60, Snr1 and E(y)3 are required for pruning of the MBγ neurons during pupal morphogenesis, while Brm and Osa are required for survival of MBγ axons during ageing. We used the courtship conditioning assay to test the effect of MB-specific SWI/SNF knockdown on short- and long-term memory. Several subunits, including Brm, Bap60, Snr1 and E(y)3, were required in the MB for both short- and long-term memory. In contrast, Osa knockdown only reduced long-term memory. Our results suggest that individual components of the SWI/SNF complex have different roles in the regulation of structural plasticity, survival and functionality of post-mitotic MB neurons. This study highlights the many possible processes that might be disrupted in SWI/SNF-related ID disorders. Our broad phenotypic characterization provides a starting point for understanding SWI/SNF-mediated gene regulatory mechanisms that are important for development and function of post-mitotic neurons.

KEYWORDS:

Drosophila melanogaster; Intellectual disability; Memory; Mushroom body; Neuron remodelling; SWI/SNF complex

PMID:
30923190
PMCID:
PMC6451433
DOI:
10.1242/dmm.037325
[Indexed for MEDLINE]
Free PMC Article

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