Myogenesis

Myogenesis is the formation of skeletal muscular tissue, particularly during embryonic development.

Muscle fibers generally form through the fusion of precursor myoblasts into multinucleated fibers called myotubes. In the early development of an embryo, myoblasts can either proliferate, or differentiate into a myotube. What controls this choice in vivo is generally unclear. If placed in cell culture, most myoblasts will proliferate if enough fibroblast growth factor (FGF) or another growth factor is present in the medium surrounding the cells. When the growth factor runs out, the myoblasts cease division and undergo terminal differentiation into myotubes. Myoblast differentiation proceeds in stages. The first stage involves cell cycle exit and the commencement of expression of certain genes.

The second stage of differentiation involves the alignment of the myoblasts with one another. Studies have shown that even rat and chick myoblasts can recognise and align with one another, suggesting evolutionary conservation of the mechanisms involved.^[1]

The third stage is the actual cell fusion itself. In this stage, the presence of calcium ions is critical. Fusion in humans is aided by a set of metalloproteinases coded for by the ADAM12 gene, and a variety of other proteins. Fusion involves recruitment of actin to the plasma membrane, followed by close apposition and creation of a pore that subsequently rapidly widens.

Novel genes and their protein products that are expressed during the process are under active investigation in many laboratories. They include:

1. Myocyte enhancer factors (MEFs), which promote myogenesis.
2. Serum response factor (SRF) plays a central role during myogenesis, being required for the expression of striated alpha-actin genes.^[2] Expression of skeletal alpha-actin is also regulated by the androgen receptor; steroids can thereby regulate myogenesis.^[3]
3. Myogenic regulatory factors (MRFs): MyoD, Myf5, Myf6 and Myogenin.