Although the mutations that result in many muscle diseases have been known for at least 20 years, progress in treating muscle disease is limited by our poor understanding of the unique cell biology that underlies skeletal muscle development and function. One of the more striking features of skeletal muscle fibers is the many nuclei that are precisely arranged at the periphery of the cell to maximize the distance between nuclei. Disruption of nuclear position is a shared amongst many muscle diseases, and is used to diagnose muscle disease. Yet how and why nuclei are positioned is not known. Using Drosophila melanogaster as a model system we have found that different disease-linked genes regulate distinct types of myonuclear movement. Furthermore, we have developed physical approaches to understand how each factor contributes to the generation of force to move nuclei and how those forces change over developmental time. Functionally, we have demonstrated that nuclear position is critical for animal locomotion because properly positioned nuclei are critical for sarcomere assembly and stability. In total, we find that the genes mutated in patients with several muscle diseases have bona fide functions in regulating nuclear position and link this function to the assembly of sarcomeres that drive muscle contraction and animal movement.
Originally published at chemistry.nd.edu.