Regulatory mechanisms for skeletal muscle differentiation and their relevance to gene expression in the heart

The discovery of the MyoD family of skeletal muscle-specific regulatory factors, which bind DNA and activate muscle-specific transcription in collaboration with widely expressed factors, has led to dramatic progress toward understanding the mechanisms responsible for activation of muscle-specific gene expression during differentiation of skeletal muscle. In contrast, relatively little is known of the mechanisms responsible for activation and maintenance of cardiac muscle transcription. Many muscle-specific genes that are directly regulated by the MyoD family in skeletal muscle are also expressed in the heart, which does not express known members of the MyoD family. The different embryonic origins of skeletal and cardiac muscle and the differences in responsiveness of skeletal and cardiac muscle-specific genes to growth factor signals suggest that, if MyoD-like proteins participate in cardiac muscle development, they are likely to be expressed much earlier in development than the MyoD family and may have diverged substantially from these skeletal muscle regulatory proteins. Regulatory pathways independent of or in addition to those controlled by MyoD-like proteins appear more likely to be involved in specification of the cardiac muscle developmental program.