Inhibition of Skeletal Muscle Development: Less Differentiation Gives More Muscle

  • Ernst-Martin Füchtbauer
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 38)


Differentiation of cells during organogenesis or regeneration is regulated by the complex interaction of signals conducting the differential activity of transcription factors. Proliferation and differentiation of cells are in many cases mutually exclusive and often seen as two opposing modes. This is particularly obvious in the development of skeletal muscle, in which myoblasts have to leave the cell cycle before they fully differentiate and fuse to become myotubes (Olson 1992). The decision of a cell to either divide or differentiate is, therefore, often the result of a competition between growth promoting factors and tissue-specific differentiation factors. However, whether a factor promotes cell proliferation or differentiation depends on the type and status of the cell that receives the signal. Differentiation of cells, e.g. fusion of myoblasts into myotubes, is often viewed as a cell’s final goal, but reaching this goal has its price. To differentiate, i.e. to cease proliferation, is a dramatic step for a cell because no daughter cells will be available to participate in the future life of the organism. For the organism as a whole, namely for an embryo, it is therefore of great importance not only to control proliferation in order to avoid neo-plastic growth, but also to fine tune differentiation in order to avoid a lack of stem cells that are needed for further development, growth and regeneration. For several reasons, inhibition of premature or ectopic differentiation seems to be especially important during myogenesis: Firstly, in the vertebrate somite the first muscle differentiation starts before the limbs even develop, yet undifferentiated cells from the somites have to migrate into the limbs and to the body wall in order to form the major muscles of the body. Secondly, muscle development proceeds in waves, where embryonic muscle fibres are followed by foetal muscle fibres, which precede neonatal muscle. Each new wave of myogenesis needs undifferentiated stem cells, which must have escaped differentiation because the pool of myogenic cells is determined early on. Thirdly, muscle has a very high regeneration capacity, which is not only needed to heal injury, but also for repair of the daily wear and tear. To fulfil these different demands for undifferentiated cells, signals are required that protect them from premature differentiation. These signals are produced either in tissues that are adjacent to myogenic cells (as the lateral plate mesoderm is adjacent to the somites) or within the population of differentiating cells. In the latter case, signalling cells might themselves become insensitive to the inhibitory signal, but protect other cells of the pool from differentiating.


Fibroblast Growth Factor Receptor C2C12 Cell Myogenic Differentiation Myogenic Cell bHLH Protein 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Ernst-Martin Füchtbauer
    • 1
  1. 1.Institute of Molecular and Structural BiologyAarhus UniversityÅrhus CDenmark

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