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Open AccessArticle

Functional Characterization of Neurofilament Light Splicing and Misbalance in Zebrafish

1
Institut Imagine, UMR-1163 INSERM et Université Paris Descartes, Hôpital Universitaire Necker-Enfants Malades, 24, boulevard du Montparnasse, 75015 Paris, France
2
Sorbonne Universités Paris VI, UMR INSERM U 1127, CNRS 1127 UPMC, Institut du Cerveau et de la Moelle épinière—ICM, 75015 Paris, France
3
Department of Neurology and Neurosurgery and Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada
4
Department of Kinesiology and Physical Education McGill University, Montreal, QC H3A 2B4, Canada
*
Author to whom correspondence should be addressed.
Current address: CNRS, UMR3738, Institut Pasteur, Department of Developmental & Stem Cell Biology, 25 rue du Dr Roux, 75015 Paris, France.
Cells 2020, 9(5), 1238; https://doi.org/10.3390/cells9051238
Received: 17 April 2020 / Revised: 8 May 2020 / Accepted: 14 May 2020 / Published: 16 May 2020
Neurofilaments (NFs), a major cytoskeletal component of motor neurons, play a key role in the differentiation, establishment and maintenance of their morphology and mechanical strength. The de novo assembly of these neuronal intermediate filaments requires the presence of the neurofilament light subunit (NEFL), whose expression is reduced in motor neurons in amyotrophic lateral sclerosis (ALS). This study used zebrafish as a model to characterize the NEFL homologue neflb, which encodes two different isoforms via a splicing of the primary transcript (neflbE4 and neflbE3). In vivo imaging showed that neflb is crucial for proper neuronal development, and that disrupting the balance between its two isoforms specifically affects the NF assembly and motor axon growth, with resultant motor deficits. This equilibrium is also disrupted upon the partial depletion of TDP-43 (TAR DNA-binding protein 43), an RNA-binding protein encoded by the gene TARDBP that is mislocalized into cytoplasmic inclusions in ALS. The study supports the interaction of the NEFL expression and splicing with TDP-43 in a common pathway, both biologically and pathogenetically. View Full-Text
Keywords: amyotrophic lateral sclerosis (ALS); neurofilament light (NEFL); TDP-43; zebrafish; neurofilaments (NFs) amyotrophic lateral sclerosis (ALS); neurofilament light (NEFL); TDP-43; zebrafish; neurofilaments (NFs)
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Demy, D.L.; Campanari, M.L.; Munoz-Ruiz, R.; Durham, H.D.; Gentil, B.J.; Kabashi, E. Functional Characterization of Neurofilament Light Splicing and Misbalance in Zebrafish. Cells 2020, 9, 1238.

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