PUBLICATION
mTOR mutation disrupts larval zebrafish tail fin regeneration via regulating proliferation of blastema cells and mitochondrial functions
- Authors
- Xiao, G., Li, X., Yang, H., Zhang, R., Huang, J., Tian, Y., Nie, M., Sun, X.
- ID
- ZDB-PUB-240530-12
- Date
- 2024
- Source
- Journal of orthopaedic surgery and research 19: 321321 (Journal)
- Registered Authors
- Keywords
- mTOR, Ca2+, Larvae fin, Mitochondrial fission, Regeneration, Zebrafish
- Datasets
- GEO:GSE242949
- MeSH Terms
-
- Animal Fins*/physiology
- Animals
- Cell Proliferation*/genetics
- Larva*/genetics
- Mitochondria*/genetics
- Mitochondria*/metabolism
- Mitochondrial Dynamics/genetics
- Mitochondrial Dynamics/physiology
- Mutation
- Regeneration*/genetics
- Regeneration*/physiology
- Signal Transduction/genetics
- TOR Serine-Threonine Kinases*/genetics
- TOR Serine-Threonine Kinases*/metabolism
- Tail*/physiology
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- PubMed
- 38812038 Full text @ J Orthop Surg Res
Citation
Xiao, G., Li, X., Yang, H., Zhang, R., Huang, J., Tian, Y., Nie, M., Sun, X. (2024) mTOR mutation disrupts larval zebrafish tail fin regeneration via regulating proliferation of blastema cells and mitochondrial functions. Journal of orthopaedic surgery and research. 19:321321.
Abstract
Background The larval zebrafish tail fin can completely regenerate in 3 days post amputation. mTOR, the main regulator of cell growth and metabolism, plays an essential role in regeneration. Lots of studies have documented the role of mTOR in regeneration. However, the mechanisms involved are still not fully elucidated.
Materials and results This study aimed to explore the role and mechanism of mTOR in the regeneration of larval zebrafish tail fins. Initially, the spatial and temporal expression of mTOR signaling in the larval fin was examined, revealing its activation following tail fin amputation. Subsequently, a mTOR knockout (mTOR-KO) zebrafish line was created using CRISPR/Cas9 gene editing technology. The investigation demonstrated that mTOR depletion diminished the proliferative capacity of epithelial and mesenchymal cells during fin regeneration, with no discernible impact on cell apoptosis. Insight from SMART-seq analysis uncovered alterations in the cell cycle, mitochondrial functions and metabolic pathways when mTOR signaling was suppressed during fin regeneration. Furthermore, mTOR was confirmed to enhance mitochondrial functions and Ca2 + activation following fin amputation. These findings suggest a potential role for mTOR in promoting mitochondrial fission to facilitate tail fin regeneration.
Conclusion In summary, our results demonstrated that mTOR played a key role in larval zebrafish tail fin regeneration, via promoting mitochondrial fission and proliferation of blastema cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping