Asymmetrical myofiber architecture along the murine tibialis anterior suggests distinct functional regions

Abstract

Skeletal muscle function is inferred from the spatial arrangement of myofiber architecture and the molecular and metabolic features of myofibers. Features of myofiber types can be distinguished by the expression of myosin heavy chain (MyHC) isoforms, indicating contraction properties. In most studies, a local sampling, typically obtained from the median part of the muscle, is used to represent the whole muscle. It remains largely unknown to what extent this local sampling represents the entire muscle. Here we studied myofiber architecture over the entire wild type mouse tibialis anterior muscle, using a high-throughput procedure combining automatic imaging and image processing analyses. We reconstructed myofiber architecture from consecutive cross-sections stained for laminin and MyHC isoforms. The data showed a marked variation in myofiber geometric features, as well as MyHC expression and the distribution of neuromuscular junctions, and suggest that muscle regions with distinct properties can be defined along the entire muscle. We show that in these muscle regions myofiber geometric properties align with biological function and propose that future studies on muscle alterations in pathological or physiological conditions should consider the entire muscle.