Related Experiment Videos
Dual Oxidase Mutant Retards Mauthner-Cell Axon Regeneration at an Early Stage via Modulating Mitochondrial Dynamics
Lei-Qing Yang1, Min Chen1, Da-Long Ren2,3
1Eye Center, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Biomedical Sciences, University of Science and Technology of China, Hefei, 230026, China.
Abstract:
Dual oxidase (duox)-derived reactive oxygen species (ROS) have been correlated with neuronal polarity, cerebellar development, and neuroplasticity. However, there have not been many comprehensive studies of the effect of individual duox isoforms on central-axon regeneration in vivo. Here, we explored this question in zebrafish, an excellent model organism for central-axon regeneration studies. In our research, mutation of the duox gene with CRISPR/Cas9 significantly retarded the single-axon regeneration of the zebrafish Mauthner cell in vivo. Using deep transcriptome sequencing, we found that the expression levels of related functional enzymes in mitochondria were down-regulated in duox mutant fish. In vivo imaging showed that duox mutants had significantly disrupted mitochondrial transport and redox state in single Mauthner-cell axon. Our research data provide insights into how duox is involved in central-axon regeneration by changing mitochondrial transport.
Insights
Dual oxidase (duox) is crucial for central nervous system axon regeneration. Its mutation impairs Mauthner cell axon regrowth in zebrafish by disrupting mitochondrial transport and redox balance.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Dual oxidase (duox) enzymes generate reactive oxygen species (ROS) linked to neuronal polarity, development, and plasticity.
- Limited in vivo studies exist on individual duox isoforms' impact on central nervous system (CNS) axon regeneration.
Purpose of the Study:
- To investigate the role of duox in CNS axon regeneration using zebrafish.
- To elucidate the molecular mechanisms by which duox influences axon regeneration.
Main Methods:
- CRISPR/Cas9 gene editing to create duox mutant zebrafish.
- Deep transcriptome sequencing to analyze gene expression changes.
- In vivo imaging to assess mitochondrial transport and redox state in Mauthner cell axons.
Main Results:
- Duox gene mutation significantly inhibited Mauthner cell axon regeneration in vivo.
- Transcriptome analysis revealed down-regulation of mitochondrial functional enzymes in duox mutants.
- In vivo imaging demonstrated disrupted mitochondrial transport and redox state in the axons of duox mutant fish.
Conclusions:
- Duox plays a critical role in central axon regeneration.
- Duox influences axon regeneration by modulating mitochondrial transport and redox state.