ZFIN ID: ZDB-PUB-200521-4
Functional Characterization of Neurofilament Light Splicing and Misbalance in Zebrafish
Demy, D.L., Campanari, M.L., Munoz-Ruiz, R., Durham, H.D., Gentil, B.J., Kabashi, E.
Date: 2020
Source: Cells   9(5): (Journal)
Registered Authors: Demy, Doris-Lou
Keywords: amyotrophic lateral sclerosis (ALS), neurofilament light (NEFL), TDP-43, neurofilaments (NFs), zebrafish
MeSH Terms:
  • Animals
  • Atrophy
  • Axons/metabolism
  • Axons/pathology
  • Cell Line
  • DNA-Binding Proteins/metabolism
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Motor Activity
  • Motor Neurons/metabolism
  • Motor Neurons/pathology
  • Phenotype
  • Polymerization
  • Postural Balance/genetics*
  • RNA Splicing/genetics*
  • Sequence Homology, Amino Acid
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 32429483 Full text @ Cells
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ABSTRACT
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.
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