Journal article
Pre- and postsynaptic upregulation of FasII synergistically underlies neuropathological and behavioral phenotypes in a Drosophila model of myotonic dystrophy
Nature communications, Vol.17(1), 1005
2026
DOI: 10.1038/s41467-025-67738-w
PMCID: PMC12847815
PMID: 41413387
Abstract
Myotonic dystrophy type 1 is a multisystemic disorder that has been extensively studied for decades, yet our understanding of its neuropathological aspect remains rudimentary. Building on an established Drosophila model, we study the neuropathological features of the disease by expressing untranslated expanded CUG repeats at the Drosophila larval neuromuscular junction. In this model, we show that both pre- and postsynaptic expressions of CUG repeats participate in inducing phenotypes in synaptic boutons, arbors, transmission and larval locomotor activity. Furthermore, expression of CUG repeats in either motorneurons or body wall muscles induces upregulation of the cell adhesion molecule FasII (NCAM1 in mammals), and the knockdown of fasII is sufficient to rescue the phenotypes. Overexpression of FasII-C, a FasII isoform with no cytoplasmic domain, mimics the phenotypes of expanded CUG expression at the neuromuscular junction. In contrary, overexpression of FasII-A-PEST+ rescues the synaptic and behavioral defects. Our study provides insights into the fundamental mechanisms underlying synapse dysregulation in myotonic dystrophy type 1.
Details
- Title: Subtitle
- Pre- and postsynaptic upregulation of FasII synergistically underlies neuropathological and behavioral phenotypes in a Drosophila model of myotonic dystrophy
- Creators
- Alex Chun Koon - Chinese University of Hong KongKa Yee Winnie Yeung - Chinese University of Hong KongYitao Wu - Chinese University of Hong KongLok I Leong - Chinese University of Hong KongJohn Tsun Po Cheung - Chinese University of Hong KongZhefan Stephen Chen - Chinese University of Hong KongShaohong Isaac Peng - Chinese University of Hong KongNoah S Armstrong - University of IowaC Andrew Frank - University of IowaPaul Magneron - Centre de Recherche en MyologieMário Gomes-Pereira - Centre de Recherche en MyologieJoyce Man See Fung - Chinese University of Hong KongAriadna Bargiela - Centro de Investigación Biomédica en RedNerea Moreno - Centro de Investigación Biomédica en RedJavier Poyatos-Garcia - Centro de Investigación Biomédica en RedJuan Vilchez - Centro de Investigación Biomédica en RedAline Huguet-Lachon - Centre de Recherche en MyologieCassandra Kussius Brewer - University of Massachusetts Chan Medical SchoolMax Zinter - University of Massachusetts Chan Medical SchoolErin S Beck - Icahn School of Medicine at Mount SinaiRubén Artero - Centro de Investigación Biomédica en RedGenevieve Gourdon - Centre de Recherche en MyologieVivian Budnik - University of Massachusetts Chan Medical SchoolTravis Thomson - University of Massachusetts Chan Medical SchoolBrian D McCabe - École Polytechnique Fédérale de LausanneHo Yin Edwin Chan - Chinese University of Hong Kong
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.17(1), 1005
- DOI
- 10.1038/s41467-025-67738-w
- PMID
- 41413387
- PMCID
- PMC12847815
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- NATURE PORTFOLIO
- Grant note
- 14102220 / Research Grants Council, University Grants Committee (RGC, UGC)
- Language
- English
- Electronic publication date
- 12/18/2025
- Date published
- 2026
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Biology
- Record Identifier
- 9985090585402771
Metrics
5 Record Views