Grant: Operating Grant

Skeletal muscle formation, or myogenesis, is a complex process controlled in large part at the transcriptional level, by a network of regulatory interactions where transcription factors (TFs) play a major role. These proteins establish various gene expression programs which enable cell fate determination, commitment to the myogenic lineage, terminal differentiation, muscle cell function, and regeneration. Multiple groups of TFs are known to be at play at each of these steps, but how they work is incompletely understood. Six1 and Six4, two members of the Six family of TFs, have been shown to play important roles in myogenesis: their function is essential to the formation of skeletal muscle, during embryonic development. However, little is known of their molecular mode of action, and their role in the function of satellite cells, the adult muscle progenitor cells, is poorly characterized. We have recently identified in a genome-wide manner direct target genes of Six1 and Six4. With this renewal proposal we seek to 1) gain a better understanding of the molecular mechanisms that regulate Six1's and Six4's target gene expression during muscle repair, and 2) apply this new knowledge to enhance the regenerative potential of muscle progenitor cells in view of cellular therapies in muscular dystrophy patients.