ArticleCommunications biology2021
Reduced C9orf72 function leads to defective synaptic vesicle release and neuromuscular dysfunction in zebrafish.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 65 citations in OpenAlex.
- PAICS mediates DNA damage and cerebellar neuronal loss in C9orf72 amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Article
- Non-Mammalian Models for Mitochondria Research in CNS Disorders.Biomolecules · 2026Review
- Unprocessed U1 snRNAs as a biomarker of INTS11- and BRAT1-related neurodevelopmental disorders.Genome medicine · 2026Article
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Article
- Synaptic Vesicle Exocytosis and Endocytosis in Motor Nerve Endings of Transgenic Mice Modeling Amyotrophic Lateral Sclerosis upon Antioxidant Treatment and Gene-Cell Therapy.Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2025Article
- Behavioral and molecular insights into anxiety in ube3a and fmr1 zebrafish models of autism spectrum disorders.Translational psychiatry · 2025Article
- Dual DNA demethylation mechanisms implement epigenetic memory driven by the pioneer factor PAX7.Science advances · 2025Article
- Cre-Lox miRNA-delivery technology optimized for inducible microRNA and gene-silencing studies in zebrafish.Nucleic acids research · 2025Article
- A zebrafish-based in vivo model of Zika virus infection unveils alterations of the glutamatergic neuronal development and NS4A as a key viral determinant of neuropathogenesis.PLoS pathogens · 2024Article
- C9orf72-Associated Dipeptide Repeat Expansions Perturb ER-Golgi Vesicular Trafficking, Inducing Golgi Fragmentation and ER Stress, in ALS/FTD.Molecular neurobiology · 2024Article
- Molecular pathology, developmental changes and synaptic dysfunction in (pre-) symptomatic human C9ORF72-ALS/FTD cerebral organoids.Acta neuropathologica communications · 2024Article
- Article
- Endocytosis of Synaptic Vesicle in Motor Nerve Endings of FUS Transgenic Mice with a Model of Amyotrophic Lateral Sclerosis.Bulletin of experimental biology and medicine · 2024Article
- Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Review
- C9ORF72 Deficiency Results in Neurodegeneration in the Zebrafish Retina.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- How do we get from hyperexcitability to excitotoxicity in amyotrophic lateral sclerosis?Brain : a journal of neurology · 2024Review
- Sensor-integrated brain-on-a-chip platforms: Improving the predictive validity in neurodegenerative research.Bioengineering & translational medicine · 2024Review
- Dietary NMN supplementation enhances motor and NMJ function in ALS.Experimental neurology · 2024Article
- Diving deep: zebrafish models in motor neuron degeneration research.Frontiers in neuroscience · 2024Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The most common genetic cause of amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) is a hexanucleotide repeat expansion within the C9orf72 gene. Reduced levels of C9orf72 mRNA and protein have been found in ALS/FTD patients, but the role of this protein in disease pathogenesis is still poorly understood. Here, we report the generation and characterization of a stable C9orf72 loss-of-function (LOF) model in the zebrafish. We show that reduced C9orf72 function leads to motor defects, muscle atrophy, motor neuron loss and mortality in early larval and adult stages. Analysis of the structure and function of the neuromuscular junctions (NMJs) of the larvae, reveal a marked reduction in the number of presynaptic and postsynaptic structures and an impaired release of quantal synaptic vesicles at the NMJ. Strikingly, we demonstrate a downregulation of SV2a upon C9orf72-LOF and a reduced rate of synaptic vesicle cycling. Furthermore, we show a reduced number and size of Rab3a-postive synaptic puncta at NMJs. Altogether, these results reveal a key function for C9orf72 in the control of presynaptic vesicle trafficking and release at the zebrafish larval NMJ. Our study demonstrates an important role for C9orf72 in ALS/FTD pathogenesis, where it regulates synaptic vesicle release and neuromuscular functions.
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