Activation and differentiation of satellite cells

Activation of satellite cells is regulated by the MyoD family of basic helix-loop-helix (bHLH) transcription factors, also called MRFs (myogenic regulatory factors) (10). This family includes MyoD and Myf5, which are expressed in determined myoblasts, as well as myogenin and MRF4, the factors that regulate terminal myogenic differentiation (reviewed in ref. 18). The expression pattern of MRFs during the activation, proliferation, and differentiation of satellite cells is analogous to the program regulating the embryonic development of skeletal muscle (Fig. 1). Resting satellite cells do not express any of the MRFs, but rapidly following activation, they start expressing either MyoD or Myf5 and follow by coexpression of MyoD and Myf5 soon after (19). Proliferation of activated satellite cells (myogenic precursor cells, MPCs) is followed by expression of myogenin and MRF4 during terminal differentiation (20).

Myof i ber

Fig. 1. Activation, proliferation, and differentiation of muscle satellite cells.

Myof i ber

Fig. 1. Activation, proliferation, and differentiation of muscle satellite cells.

Satellite cells appear to be able both to self-renew and to proliferate and contribute to a certain tissue type. These two functions are regulated by distinct mechanisms, as illustrated by the analysis of satellite cells from the MyoD-/- knockout mice (21). Skeletal muscle from these mice has a severely reduced capacity for regeneration, even though there are more satellite cells. These differences become even more striking when the MyoD-/- mice are interbred with mdx mice, the animal model for Duchenne muscular dystrophy. In the double-mutant mice, the number of satellite cells exceeds the wild-type 13-fold, yet there is pronounced muscle atrophy and absence of regeneration (22). These results suggest that, in vivo, upregulation of MyoD is required for satellite cells to enter the MPC proliferative phase that precedes terminal differentiation. In the absence of MyoD, satellite cells seem to demonstrate an increased ability to self-renew and a decreased differentiation potential.

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