Reprogramming miR-146b-snphb Signaling Activates Axonal Mitochondrial Transport in the Zebrafish M-cell and Facilitates Axon Regeneration After Injury
Xin‑Liang Wang2 · Zong‑Yi Wang2 · Xing‑Han Chen2 · Yuan Cai3 · Bing Hu1,21 Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
2 Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China
3 First Afliated Hospital of USTC, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
Abstract
Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration. Syntaphilin (Snph), known for its potent mitochondrial anchoring action, has emerged as a significant inhibitor of both mitochondrial transport and axonal regeneration. Therefore, investigating the molecular mechanisms that influence the expression levels of the snph gene can provide a viable strategy to regulate mitochondrial trafficking and enhance axonal regeneration. Here, we reveal the inhibitory effect of microRNA-146b (miR-146b) on the expression of the homologous zebrafish gene syntaphilin b (snphb). Through CRISPR/Cas9 and single-cell electroporation, we elucidated the positive regulatory effect of the miR-146b-snphb axis on Mauthner cell (M-cell) axon regeneration at the global and single-cell levels. Through escape response tests, we show that miR-146b-snphb signaling positively regulates functional recovery after M-cell axon injury. In addition, continuous dynamic imaging in vivo showed that reprogramming miR-146b significantly promotes axonal mitochondrial trafficking in the pre-injury and early stages of regeneration. Our study reveals an intrinsic axonal regeneration regulatory axis that promotes axonal regeneration by reprogramming mitochondrial transport and anchoring. This regulation involves noncoding RNA, and mitochondria-associated genes may provide a potential opportunity for the repair of central nervous system injury.
Keywords
Syntaphilin b; MicroRNA-146b; Axon regeneration; Axonal mitochondrial transport; Single-cell electroporation; Zebrafsh
