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24 October 2018

Study sets a new milestone in the understanding of muscle formation

Researchers from the Randall Centre for Cell & Molecular Biophysics believe they have reached a new milestone in the understanding of muscle formation that could help define new cellular and molecular approaches in pathological conditions affecting muscle wellness.

muscle fibres

Each muscle is composed of bundles of individual muscle fibres capable of physical contraction. To grow large and strong, each fibre is formed by the fusion of several muscle precursor cells in a process called myogenesis.

During myogenesis, the muscle transcription factor Myogenin plays a pivotal role in orchestrating the expression of other muscle-specific genes.  

Almost 25 years ago, two publications (Nabeshima et al Nature 1993 and Hasty et al Nature 1993) showed that the lack of Myogenin blocked proper myogenesis in a mouse model. Since that time, no studies have identified a specific cellular or molecular function for Myogenin during myogenesis.

To gain insight into Myogenin function the team used the zebrafish as an animal model and created a mutant in which the expression of Myogenin protein was abolished.

In a paper published in Nature Communications, the authors found that Myogenin is a master regulator of muscle cell fusion, therefore controlling the formation of functional muscle fibres and sustaining normal muscle growth during both embryonic and adult muscle development. 

Their findings also revealed that another molecule, named Hedgehog, promotes the formation of multinucleated muscle fibres via a second, Myogenin-independent, pathway.

The authors hope these findings will allow them to make progress in understanding how the correct number of muscle fibres with the right sizes are formed in the body.  

Co-authors on the paper Dr Massimo Ganassi and Professor Simon Hughes believe that this may provide insight into how to repair sick or injured muscle and maintain muscle mass in the elderly and disease conditions.