Functional characterization of Neurofilament Light b splicing and misbalance in zebrafish

Demy, D. L.; Campanari, M.-L.; Munoz-Ruiz, R.; Durham, H. D.; Gentil, B.; Kabashi, E.

doi:10.1101/2020.04.27.064063

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bioRxiv · 10.1101/2020.04.27.064063

Functional characterization of Neurofilament Light b splicing and misbalance in zebrafish

Demy, D. L.·Campanari, M.-L.·Munoz-Ruiz, R.·Durham, H. D.·Gentil, B.·Kabashi, E.

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Abstract

Neurofilaments (NFs), a major cytoskeletal component of motor neurons, play a key role in their 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, which 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 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 NF assembly and motor axon growth, with resulting motor deficits. This equilibrium is also disrupted upon partial depletion of TDP-43, a RNA binding protein that is mislocalized into cytoplasmic inclusions in ALS. The study supports interaction of NEFL expression and splicing with TDP-43 in a common pathway, both biologically and pathogenetically.

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Demy, D. L., Campanari, M.-L., Munoz-Ruiz, R., Durham, H. D., Gentil, B., Kabashi, E.. 2020-04-28. Functional characterization of Neurofilament Light b splicing and misbalance in zebrafish. https://doi.org/10.1101/2020.04.27.064063

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