Functional Characterization of Neurofilament Light Splicing and Misbalance in Zebrafish
| Autor: | Benoit J. Gentil, María Letizia Campanari, Edor Kabashi, Raphael Munoz-Ruiz, Doris Lou Demy, Heather D. Durham |
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| Přispěvatelé: | Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gene isoform Embryo Nonmammalian Neurofilament amyotrophic lateral sclerosis (ALS) TDP-43 RNA Splicing [SDV]Life Sciences [q-bio] Motor Activity Primary transcript TARDBP Article Cell Line Polymerization 03 medical and health sciences 0302 clinical medicine neurofilament light (NEFL) neurofilaments (NFs) Neurofilament Proteins Animals Humans Cytoskeleton Intermediate filament Postural Balance lcsh:QH301-705.5 Zebrafish Motor Neurons Sequence Homology Amino Acid biology Chemistry Gene Expression Regulation Developmental General Medicine Zebrafish Proteins biology.organism_classification zebrafish Axons Cell biology DNA-Binding Proteins [SDV] Life Sciences [q-bio] Phenotype 030104 developmental biology lcsh:Biology (General) RNA splicing Atrophy amyotrophic lateral sclerosis (ALS) neurofilament light (NEFL) TDP-43 030217 neurology & neurosurgery |
| Zdroj: | Cells Cells, MDPI, 2020, 9 (5), pp.1238. ⟨10.3390/cells9051238⟩ Cells, Vol 9, Iss 1238, p 1238 (2020) Cells, 2020, 9 (5), pp.1238. ⟨10.3390/cells9051238⟩ Volume 9 Issue 5 |
| ISSN: | 2073-4409 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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