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bioRxiv · 10.64898/2026.01.22.701008

A Spinal Muscular Atrophy Model Reveals Both Developmental and Degenerative Neuronal Defects in C. elegans

Savaheli, S.·Gallotta, I.·Santonicola, P.·Cieri, F.·Berger, S.·Dargere, D.·Di Schiavi, E.·Dupuy, D.
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Abstract

Spinal muscular atrophy (SMA) is a neuromuscular disorder primarily caused by mutations in the Survival of Motor Neuron 1 (SMN1) gene. SMN1 is ubiquitously expressed and encodes a protein essential for the assembly of small nuclear ribonucleoproteins (snRNPs), key components of pre-mRNA splicing. Beyond this canonical role, SMN participates in several other fundamental cellular processes, including RNA transport, regulation of actin dynamics, transcription, and translation. While multiple hypotheses have been put forward to explain selective motor neuron (MN) vulnerability to SMN deficiency, the precise mechanisms involved remain incompletely understood. In this study, we used a simple and tractable C. elegans model to investigate the molecular mechanisms underlying neuronal degeneration in SMA. Silencing of the smn-1 in targeted neurons resulted in defects in the birth and development of both motor neurons and touch receptor neurons (TRNs). In TRNs SMN-1 depletion caused distinct defects in neuronal process morphology. Our results provide evidence that key aspects of SMA pathology are conserved in C. elegans, which may offer new opportunities to elucidate the molecular mechanisms underlying neuronal degeneration in SMA.

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Savaheli, S., Gallotta, I., Santonicola, P., Cieri, F., Berger, S., Dargere, D., Di Schiavi, E., Dupuy, D.. 2026-01-24. A Spinal Muscular Atrophy Model Reveals Both Developmental and Degenerative Neuronal Defects in C. elegans. https://doi.org/10.64898/2026.01.22.701008

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