Figure 9

Summary of the present work concerning the fiber type specification under the control of Sox6. It has been shown that in zebrafish, MyoD and Myf5 are necessary to activate Sox6 gene expression in muscle [100]. This muscle-specific Sox6 activation mechanism has not been tested in mice yet, but since Sox6 upregulation coincides with upregulation of these myogenic regulatory factors during muscle differentiation, it is very likely that this mechanism is shared in mice also (see text). Once expressed in muscle, Sox6 directly suppresses transcription of slow fiber specific, cardiac and embryonic isoform genes during muscle development. In addition to these structural protein genes, Sox6 suppresses expression of the transcription factors which have been shown to activate slow fiber specific genes, Tead1, Tead4, and Prox1. By unknown mechanisms, fast fiber-specific gene expression in Sox6 KO skeletal muscle is dramatically reduced. Since Sox6 is preferentially expressed in fast-twitch fiber rich muscles, it is possible that Sox6 indirectly stimulates the fast fiber-specific gene program. This idea awaits future investigation. Sox6 activity in slow fibers is suppressed by miR-499 which is encoded in an intron of the Myh7b gene. We have shown that Sox6, in turn, suppresses Myh7b transcription. This negative feedback loop might be important for fiber type switching during muscle development as well as in adult muscle.