A structural transition ensures robust formation of skeletal muscle

Abstract

During organ development cells undergo significant morphological and positional changes. Yet, by the end of organogenesis, internal organ structure is typically robustly defined, with cells tightly packed. It remains an open question as to how the three-dimensional (3D) internal structure of an organ emerges reliably, particularly when there are multiple cell types interacting and dynamic boundary constraints. Here, we utilise quantitative live imaging and 3D morphological measures of the developing zebrafish myotome to unravel how early muscle organisation emerges. Contrary to the textbook view of muscle fibres as cylindrical, myocytes undergo an ordered chiral twist, the direction and magnitude of which depends on their position within the myotome. Further, cells skew and rearrange, seemingly to facilitate close packing of neighbouring muscle fibres. Cell movement undergoes a rapid decline in speed once the cells span the myotome segment. We find that cell packing is altered in mutants that disrupt cell fate or cell fusion, even though the final muscle segments remain largely confluent. Biophysical perturbation reveals that the cells are mechanically plastic, able to adjust to changes in the local cellular environment and boundary constraints. Taking these results together, we propose that the early myotome undergoes a structural transition, from a fluid-like state into a frozen state, resembling glass-like behaviour. Cellular plasticity in response to varying boundary constraints may be a general mechanism for ensuring robust organ morphogenesis in dense 3D tissues.