MYOGENESIS AND MYOPATHIES

Transcription factors are part of the machinery that decides which genes should be active and which silent. In this way, transcription factors have a strong impact on embryonic development. Skeletal muscle development is an excellent process to study the roles of transcription factors in vitro and in vivo. The development of skeletal muscle is a complex process which has been highly conserved in evolution. It involves cell specification, tissue rearrangement and differentiation (Buckingham 2001, 2006; Brand-Saberi 2005). These steps are all tightly controlled by a number of signaling molecules and transcription factors that have been put into an increasingly complex hierarchy during recent years. In this hierarchy, the paired box transcription factor Pax3 has been attributed a key role upstream of some of the important key factors of the bHLH family of myogenic regulatory factors (Tajbakhsh et al. 1997).
More recently, members of the sine oculis/Six gene family, Six1 and Six4 have been shown to have an important function in myogenesis upstream of Pax3 and the MRFs (Grifone et al. 2005). Six1 and Six4 encode homeoprotein transcription factors.
In the human, disturbances in skeletal muscle development and maintenance cause congenital myopathies that show a wide variety of clinical manifestations and progression of the symptoms. Quite often the aetiology of congenital myopathies remains obscure and the disorders are not yet curable by available therapies. The congenital myopathies are characterized by structural and histochemical anomalies such as muscle fibre disproportions or protein aggregations. The histological variety is in accordance with their clinical appearance, which ranges from mild to very severe myopathies with perinatal respiratory failure. Some known causes of myopathies include defects of membranous proteins, enzymes or structural proteins (Bornemann and Goebel, 2001). We have recently focused on the study of bHLH and other transcription factors which have been shown to play a decisive role in tissue specification during development.

Satellite cell marked by Pax7 immunostaining (green) of a EDL myofiber from mouse embryos.

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