# Dynamic expression and differential requirement of the myocyte fusogen Myomixer during distinct myogenic episodes in the zebrafish

## TL;DR

The study shows how Myomixer helps form muscle fibers in zebrafish and how its absence affects muscle and bone development.

## Contribution

The paper reveals dynamic Myomixer expression and distinct roles in muscle formation across zebrafish life stages.

## Key findings

- Myomixer expression varies spatially and temporally during early muscle development.
- Loss of Myomixer disrupts myotome structure and alters segment shape.
- Myomixer and Myomaker have different impacts on muscle growth and fusion.

## Abstract

Skeletal muscle formation involves the fusion of myocytes into precisely aligned, multinucleated myofibres. These fibres continue to grow through reiterative rounds of myocyte fusion, incorporating new myonuclei and supporting muscle growth, repair and regeneration over organismal life span. The vertebrate-specific myocyte fusogens, Myomaker (Mymk) and Myomixer (Mymx), are crucial for generating multinucleated skeletal muscles. Here, using quantitative imaging and a mymx knockout strain, we explored the impact on myogenesis at different life stages of the zebrafish. We demonstrate that during the initial phase of muscle formation, mymx has a spatiotemporally varied expression across all axes of the developing myotome, not just along the anterior-posterior axis. On Mymx loss, myotome morphogenesis is disrupted, with both cell and tissue structure impacted. In particular, the shape of the resulting myotome segments is altered. Moreover, we show differential effects of Mymk versus Mymx loss on myocyte fusion and muscle growth. Finally, we report that perturbation to adult muscle multinucleation and size impacted bone development, again with different phenotypic severities among the two fusogen mutants. Together, our work provides insights into the interplay between myocyte fusion, myotome morphogenesis and acquisition of final adult form.

Summary: Myocyte fusion is essential for muscle development, and fusion defects cause myopathies in humans. Dhar et al. describe dynamic expression and function of the myocyte fusogen, Myomixer, during zebrafish myogenesis.