Role of Membrane Fluctuations and Tension in Cell Fusion During Myogenesis

Myogenesis is the formation of adult skeletal muscle from muscle precursor cells. Muscle tissues make up the largest body tissues in an organism. Skeletal muscle is essential for locomotion, and movement and is voluntarily controlled by the organism, unlike cardiac and smooth muscle. It has a highly organized cytoskeletal system. One of the distinct characteristics of skeletal muscle is the striation contributed by the repeating unit of actin and myosin, together they form a single myofiber. This repeating unit of actin and myosin, known as sarcomere, establishes the skeletal muscle unit.

If we investigate the developmental origin of skeletal muscle, it starts from the paraxial mesoderm. Paraxial mesoderm is a tissue formed in blastopore or primitive streak during the process of gastrulation. During embryo axis elongation, at the posterior tip of the embryo paraxial mesoderm forms presomitic mesoderm. The anterior part of the transient presomitic mesoderm structure is committed to form somite. It is the somite from where myogenesis starts. Initiated with skeletal myoblast cells, myogenesis involves proliferation and differentiation which ultimately leads to the formation of multinucleated myofibers by the fusion of mononucleated myoblasts and myocytes.

A vast number of transcription factors control the process of myogenesis. These factors are known as myogenic regulatory factors (MRFs) and are member of basic helix loop helix family transcription factors. Activation of these MRFs is the hallmark of the initiation of myogenesis. Here we discussed different factors that contributed to the various stages of myogenesis starting from the embryonic stage to tissue formation. In general, muscle development has two major phases, one is embryonic developmental phase from where skeletal muscle tissue develops and another is muscle regeneration which is more prominent in adult muscle tissue after facing injury. Both development and regeneration need regulation by MRFs.

The analysis of cell fusion and the mechanism behind it started long back in different systems. Starting from the embryonic stages we have found cell fusion as a normal physiological phenomenon in neural cell, yeast reproduction, exocytosis, macrophage, and muscle cells. Here, we addressed the fusion of mouse myoblasts where two or more myoblast cells fused to form multinucleated myotubes. Apart from the vertebrate system, mechanism of myoblast fusion has also been established in Drosophila and zebrafish systems. Despite the differences in gene expression, the fundamental mechanism of muscle fusion remains the same across systems.