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Loss of Myomixer Results in Defective Myoblast Fusion, Impaired Muscle Growth, and Severe Myopathy in Zebrafish
Ist Teil von
Marine biotechnology (New York, N.Y.), 2022-10, Vol.24 (5), p.1023-1038
Ort / Verlag
New York: Springer US
Erscheinungsjahr
2022
Quelle
MEDLINE
Beschreibungen/Notizen
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.