Slow muscles guide fast myocyte fusion to ensure robust myotome formation despite the high spatiotemporal stochasticity of fusion events

Skeletal myogenesis is dynamic, and it involves cell-shape changes together with cell fusion and rearrange-ments. However, the final muscle arrangement is highly organized with striated fibers. By combining live imaging with quantitative analyses, we dissected fast-twitch myocyte fusion within the zebrafish myotome in toto. We found a strong mediolateral bias in fusion timing; however, at a cellular scale, there was het-erogeneity in cell shape and the relationship between initial position of fast myocytes and resulting fusion partners. We show that the expression of the fusogen myomaker is permissive, but not instructive, in deter-mining the spatiotemporal fusion pattern. Rather, we observed a close coordination between slow muscle rearrangements and fast myocyte fusion. In mutants that lack slow fibers, the spatiotemporal fusion pattern is substantially noisier. We propose a model in which slow muscles guide fast myocytes by funneling them close together, enhancing fusion probability. Thus, despite fusion being highly stochastic, a robust myotome structure emerges at the tissue scale.

Automated summary

The process of skeletal myogenesis involves dynamic changes in cell shape, fusion, and rearrangement, leading to the organized structure of striated fibers. Through live imaging and quantitative analysis in zebrafish, the fusion of fast-twitch myocytes within the myotome was studied. It was found that fusion timing had a strong medial-lateral bias, while at the cellular scale, there was heterogeneity in cell shape and the relationship between initial position and fusion partners. The study suggests that slow muscle rearrangement guides the fusion of fast myocytes, enhancing fusion probability and contributing to the emergence of a robust myotome structure.