PUBLICATION
Loss of Myomixer Results in Defective Myoblast Fusion, Impaired Muscle Growth, and Severe Myopathy in Zebrafish
- Authors
- Wu, P., Yong, P., Zhang, Z., Xu, R., Shang, R., Shi, J., Zhang, J., Bi, P., Chen, E., Du, S.
- ID
- ZDB-PUB-220911-24
- Date
- 2022
- Source
- Marine biotechnology (New York, N.Y.) 24(5): 1023-1038 (Other)
- Registered Authors
- Du, Shao Jun (Jim)
- Keywords
- Hedgehog, Myoblast fusion, Myomixer, Zebrafish
- MeSH Terms
-
- Mice
- Muscle Proteins/genetics
- Animals
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Hedgehog Proteins/genetics
- Hedgehog Proteins/metabolism
- Muscular Diseases*/genetics
- Muscular Diseases*/metabolism
- Humans
- Muscle, Skeletal/metabolism
- Membrane Proteins/genetics
- Myoblasts/metabolism
- PubMed
- 36083384 Full text @ Mar. Biotechnol.
Citation
Wu, P., Yong, P., Zhang, Z., Xu, R., Shang, R., Shi, J., Zhang, J., Bi, P., Chen, E., Du, S. (2022) Loss of Myomixer Results in Defective Myoblast Fusion, Impaired Muscle Growth, and Severe Myopathy in Zebrafish. Marine biotechnology (New York, N.Y.). 24(5):1023-1038.
Abstract
The development and growth of fish skeletal muscles require myoblast fusion to generate multinucleated myofibers. While zebrafish fast-twitch muscle can fuse to generate multinucleated fibers, the slow-twitch muscle fibers remain mononucleated in zebrafish embryos and larvae. The mechanism underlying the fiber-type-specific control of fusion remains elusive. Recent genetic studies using mice identified a long-sought fusion factor named Myomixer. To understand whether Myomixer is involved in the fiber-type specific fusion, we analyzed the transcriptional regulation of myomixer expression and characterized the muscle growth phenotype upon genetic deletion of myomixer in zebrafish. The data revealed that overexpression of Sonic Hedgehog (Shh) drastically inhibited myomixer expression and blocked myoblast fusion, recapitulating the phenotype upon direct genetic deletion of myomixer from zebrafish. The fusion defect in myomixer mutant embryos could be faithfully rescued upon re-expression of zebrafish myomixer gene or its orthologs from shark or human. Interestingly, myomixer mutant fish survived to adult stage though were notably smaller than wildtype siblings. Severe myopathy accompanied by the uncontrolled adipose infiltration was observed in both fast and slow muscle tissues of adult myomixer mutants. Collectively, our data highlight an indispensable role of myomixer gene for cell fusion during both embryonic muscle development and post-larval muscle growth.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping