Reorganization of Septin structures regulates early myogenesis

Abstract Controlled myogenic differentiation is crucial for developmental formation, homeostatic maintenance and adult repair of skeletal muscle and relies on cell fate determinants in myogenic progenitors or resident stem cells. Proliferating muscle progenitors migrate, adopt spindle shape, align membranes and fuse into multinuclear syncytia. These processes are accompanied by cyto-architectural changes driven by rearranging of cytoskeletal components such as actin and microtubules. Here we highlight septins, the fourth component of the cytoskeleton, to represent an essential structural element of myoblasts. Specifically, Septin9 regulates myoblast differentiation during the early commitment process. Depletion of Septin9 in C2C12 cells and primary myoblasts led to a precocious switch from a proliferative towards a committed progenitor transcriptomic program. Additionally, we report Septin9 undergoing substantial reorganization and downregulation during myogenic differentiation. Together, we propose filamentous septin structures and their controlled reorganization in myoblasts to provide a key temporal regulation mechanism for the differentiation of myogenic progenitors.