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bioRxiv · 10.1101/2023.05.19.541505

Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair.

Muraleedharan Saraswathy, V.·Zhou, L.·Mokalled, M. H.
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Abstract

Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during spinal cord repair. Neurogenesis of glutamatergic and GABAergic neurons restores the excitatory/inhibitory balance after injury. In addition, a transient population of injury-responsive neurons (iNeurons) show elevated plasticity between 1 and 3 weeks post-injury. We found iNeurons are injury-surviving neurons that acquire a neuroblast-like gene expression signature after injury. CRISPR/Cas9 mutagenesis showed iNeurons are required for functional recovery and employ vesicular trafficking as an essential mechanism that underlies neuronal plasticity. This study provides a comprehensive resource of the cells and mechanisms that direct spinal cord regeneration and establishes zebrafish as a model of plasticity-driven neural repair.

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Muraleedharan Saraswathy, V., Zhou, L., Mokalled, M. H.. 2023-05-22. Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair.. https://doi.org/10.1101/2023.05.19.541505

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