Seminar

The way shape of organs and embryos emerges and self-organize during development has been a fundamental question in biology. Myogenesis, the formation of skeletal muscle tissue, is a key process during embryonic development. Myoblast fusion where individual myoblasts merge to form myotubes is critical for myogenesis during embryonic development as well as for muscle repair in the adult. Myoblast fusion is a complex process that relies on cell-cell interaction, cell adhesion, and cytoskeletal remodeling and membrane fusion. Despite numerous studies on the signals and the downstream effectors implicated in myoblast fusion, its mechanical regulation remains an open question. Here, we investigated this question by observing primary myoblasts cultured on deformable substrates and show that myoblasts rearrange and realign themselves to form long oriented domains that leads to singularities (topological defects). We observed that fusion of myoblasts cells are primarily associated with the locations of singularities that correspond to hotspots of high compressive stresses. As the system evolves over time through the process of fusion that result in growth of the myotubes, the number of defects decrease by annihilation followed by long-range cellular alignment. These results are accompany by a considerable increase in isotropic stresses. By impairing fusion and myotube growth through biochemical perturbations, we show that these effects are reversed, demonstrating the role of myotube growth in the self-organization of the cell population. Altogether, our results highlights the crucial importance of the physical properties of cell populations and mechanical forces in regulating complex morphogenic events.