The molecular regulation of myogenesis

Over the past years, several studies have unraveled important mechanisms by which the four myogenic regulatory factors (MRFs: MyoD, Myf-5. myogenin, a nd MRF4) control the specification and the differentiation of the muscle li neage. Early experiments led to the hypothesis that these factors were redu ndant and could functionally replace one another. However, recent experimen ts using in vivo and in vitro models have demonstrated that in fact differe nt aspects of the myogenic program are controlled by different factors in v ivo, suggesting that these factors play distinct roles juring myogenesis. T he activity of the MRFs during proliferation and differentiation of muscle precursor cells has clearly been demonstrated to be dependent on specific c ell-cycle control mechanisms as well as distinct interactions with other re gulatory molecules, such as the ubiquitously expressed E proteins and sever al other transcription factors, Furthermore, the observation that the MRFs can recruit chromatin remodeling proteins has shed some light on the mechan isms by which the MRFs activate gene expression. Recently, a functional rol e for MyoD during satellite cell activation and muscle repair has been iden tified bt vivo, which cannot be substituted for by the other MRFs. This has put forward the hypothesis that these factors also play specific biologica l roles following muscle injury and repair.