Myomaker protein proves essential for muscle regeneration
A new scientist at Cincinnati Children’s is beginning to unlock the genetic secrets of muscle cell fusion, an advance that could have extensive implications for health.
While working as a post-doctoral fellow at the University of Texas Southwestern in Dallas, Doug Millay, PhD, and his mentor found the only muscle-specific protein known to be essential for fusion of embryonic and adult myoblasts. In a paper published in 2013 in Nature, they dubbed the gene “myomaker.” Then in a more recent paper in Genes and Development, the team showed that myomaker also is necessary for normal adult muscle cell regeneration.
Their work shows that myogenic basic helix–loop–helix (bHLH) transcription factors induce myomaker expression in satellite cells during acute and chronic muscle regeneration. Moreover, genetic deletion of myomaker in adult satellite cells completely abolishes muscle regeneration, resulting in severe muscle destruction after injury.
The ability of myomaker to promote fusion to adult muscle fibers and muscle regeneration suggests opportunities to enhance muscle repair through myomaker-directed cell–cell fusion. In mice, the myomaker gene can be expressed on non-muscle cells, which then allows these cells to fuse to skeletal muscle. This implies that myomaker might be useful as a delivery vehicle for future therapies to address muscle loss in Duchenne muscular dystrophy, cancer, AIDS, and COPD.
“In all of these conditions, restoring muscle cell growth may likely do even more than impact quality of life,” Millay says. “It could also slow the progression of the disease itself.”
Millay is one of two scientists at Cincinnati Children’s to be named Pew Scholars in 2015. He is continuing his work to more fully understand the machinery of muscle cell development.
