| Title: |
Pre- and postsynaptic upregulation of FasII synergistically underlies neuropathological and behavioral phenotypes in a Drosophila model of myotonic dystrophy |
| Authors: |
Koon, Alex Chun; Yeung, Ka Yee Winnie; Wu, Yitao; Leong, Lok I; Cheung, John Tsun Po; Chen, Zhefan Stephen; Peng, Shaohong Isaac; Armstrong, Noah S; Frank, C Andrew; Magneron, Paul; Gomes-Pereira, Mário; Fung, Joyce Man See; Bargiela, Ariadna; Moreno, Nerea; Poyatos-Garcia, Javier; Vilchez, Juan; Huguet-Lachon, Aline; Brewer, Cassandra Kussius; Zinter, Max; Beck, Erin S; Artero, Rubén; Gourdon, Genevieve; Budnik, Vivian; Thomson, Travis; McCabe, Brian D; Chan, Ho Yin Edwin |
| Contributors: |
Neurobiology; Thomson Lab |
| Source: |
Nature communications ; England |
| Publication Year: |
2025 |
| Collection: |
University of Massachusetts, Medical School: eScholarship@UMMS |
| Description: |
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. ; No embargo |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Nature Communications; https://doi.org/10.1038/s41467-025-67738-w; https://hdl.handle.net/20.500.14038/55008 |
| DOI: |
10.1038/s41467-025-67738-w |
| Availability: |
https://doi.org/10.1038/s41467-025-67738-w; https://hdl.handle.net/20.500.14038/55008 |
| Rights: |
© The Author(s) 2025. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.37632DFB |
| Database: |
BASE |