microRNA-2184 orchestrates Mauthner-cell axon regeneration in zebrafish via syt3 modulation

J Genet Genomics. 2024 Apr 4:S1673-8527(24)00069-9. doi: 10.1016/j.jgg.2024.03.016. Online ahead of print.

Abstract

MicroRNAs (miRNAs) play a significant role in axon regeneration following spinal cord injury. However, the functions of numerous miRNAs in axon regeneration within the central nervous system (CNS) remain largely unexplored. Here, we elucidate the positive role of miR-2184 in axon regeneration within zebrafish Mauthner cells (M-cells). The upregulation of miR-2184 in the single M-cells facilitates axon regeneration, while the specific sponge-induced silencing of miR-2184 leads to impeded axon regeneration. We show that syt3, a downstream target of miR-2184, negatively regulates axon regeneration, and the regeneration suppression by syt3 depends on its binding to Ca2+. Furthermore, pharmacological stimulation of the cAMP/PKA pathway suggests that changes in the readily releasable pool may affect axon regeneration. Our data indicate that miR-2184 promotes axon regeneration of M-cells within the CNS by modulating the downstream target syt3, providing valuable insights into potential therapeutic strategies.

Keywords: Axon ablation; Axon regeneration; RRP; miRNA-2184; syt3.