PUBLICATION
Requirement of the fusogenic micropeptide myomixer for muscle formation in zebrafish
- Authors
- Shi, J., Bi, P., Pei, J., Li, H., Grishin, N.V., Bassel-Duby, R., Chen, E.H., Olson, E.N.
- ID
- ZDB-PUB-171029-5
- Date
- 2017
- Source
- Proceedings of the National Academy of Sciences of the United States of America 114(45): 11950-11955 (Journal)
- Registered Authors
- Keywords
- fusogenic, micropeptide, myogenesis, myomaker, zebrafish
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- CRISPR-Cas Systems/genetics
- Cell Fusion
- Cell Line
- Elephants/genetics
- Membrane Proteins/genetics*
- Muscle Development/genetics*
- Muscle Development/physiology
- Muscle Fibers, Skeletal/cytology*
- Muscle Proteins/genetics*
- Myoblasts/metabolism*
- Sharks/genetics
- Turtles/genetics
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- PubMed
- 29078404 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Shi, J., Bi, P., Pei, J., Li, H., Grishin, N.V., Bassel-Duby, R., Chen, E.H., Olson, E.N. (2017) Requirement of the fusogenic micropeptide myomixer for muscle formation in zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 114(45):11950-11955.
Abstract
Skeletal muscle formation requires fusion of mononucleated myoblasts to form multinucleated myofibers. The muscle-specific membrane proteins myomaker and myomixer cooperate to drive mammalian myoblast fusion. Whereas myomaker is highly conserved across diverse vertebrate species, myomixer is a micropeptide that shows relatively weak cross-species conservation. To explore the functional conservation of myomixer, we investigated the expression and function of the zebrafish myomixer ortholog. Here we show that myomixer expression during zebrafish embryogenesis coincides with myoblast fusion, and genetic deletion of myomixer using CRISPR/Cas9 mutagenesis abolishes myoblast fusion in vivo. We also identify myomixer orthologs in other species of fish and reptiles, which can cooperate with myomaker and substitute for the fusogenic activity of mammalian myomixer. Sequence comparison of these diverse myomixer orthologs reveals key amino acid residues and a minimal fusogenic peptide motif that is necessary for promoting cell-cell fusion with myomaker. Our findings highlight the evolutionary conservation of the myomaker-myomixer partnership and provide insights into the molecular basis of myoblast fusion.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping