Although the common notion `movement is life and stagnancy is death' is not entirely correct, we know that muscles are essential to animal life. They facilitate motility in search of sex and food, ensure the circulation of blood and air, and drive the functions of internal organs such as glands, intestines and bladders. Three different types of muscles are involved in these processes in vertebrates: smooth, cardiac and skeletal muscles. Skeletal muscles are composed of repetitive contractile units that are arranged in a highly ordered manner. Muscle fibres originate from progenitor cells, called myoblasts, which fuse during development into myotubes – muscle fibres' embryonic ancestors. Ultimately, muscle fibres are made up of sarcomeres, comprised of actin and myosin filaments, which are the muscle's ATP fuelled contractile elements. Development of such a complex structure can be described as an opera in two acts. The first act presents myoblast differentiation and fusion to form myotubes; the second act stages further differentiation steps including the assembly of the sarcomeres. But how is the complex cyto-architecture of muscle fibres achieved during development? What are the regulatory principles,and which factors are involved in sarcomere formation? Recent studies performed in insects have provided important answers to some of these questions, and a team of British scientists, led by John Sparrow, have recently revealed new insights into the molecular details of myofibril assembly and its relationship with the regulation of muscle contraction.
In order to study myofibril assembly, Sparrow and his colleagues established a unique genetic system using Drosophila indirect flight muscles, which allows in vivo investigation of myogenesis. Aware of the muscle cell's developmental path, the team addressed two major issues: (1)does troponin I, which is part of a regulatory complex inhibiting muscle contraction in the absence of Ca2+, play a role in sarcomere formation, and (2) do actin–myosin interactions affect myofibril assembly?
To answer these questions, the scientists analysed several Drosophila mutants with defects in the biosynthesis of sarcomeric proteins. When they investigated null mutants lacking either actin or myosin,they found that the insects had normal muscle fibre morphology, indicating that neither actin, nor myosin, is necessary for myoblast fusion or subsequent differentiation events. In other words, fibre morphogenesis does not require sarcomere assembly.
By contrast, fibre morphogenesis and sarcomere formation do seem to depend on the interaction of sarcomeric proteins. When the scientists looked at a homozygote null mutant lacking functional troponin I, they found muscle degeneration with defects in sarcomere formation. Since troponin I is part of the muscle contraction regulatory complex, another question manifested itself. The team reasoned that in the absence of troponin I, unregulated muscle contractions caused by actin–myosin interactions must occur during assembly. Hence the question: are these interactions responsible for the mutant's phenotype? To answer this question, the British team crossed a heterozygote troponin I mutant with a fly strain expressing modified myosin that can assemble into filaments but cannot interact with actin filaments to produce force. Surprisingly, they found that muscle degeneration and the defects in sarcomere formation were suppressed, indicating the need for inhibition of muscle contractions by troponin I during development.
Although many important questions of myogenesis are still unsolved, it is clear now that fibre morphogenesis and sarcomere formation are separate and independent processes requiring the inhibition of muscle contraction.
