Myogenic regulatory factors: redundant or specific functions? Lessons from Xenopus

The discovery, in the late 1980s, of the MyoD gene family of muscle transcription factors has proved to be a milestone in understanding the molecular events controlling the specification and differentiation of the muscle lineage. From gene knock-out mice experiments progressively emerged the idea that each myogenic regulatory factor (MRF) has evolved a specialized as well as a redundant role in muscle differentiation. To date, MyoD serves as a paradigm for the MRF mode of function. The features of gene regulation by MyoD support a model in which subprograms of gene expression are achieved by the combination of promoter-specific regulation of MyoD binding and MyoD-mediated binding of various ancillary proteins. This binding likely includes site-specific chromatin reorganization by means of direct or indirect interaction with remodeling enzymes. In this cascade of molecular events leading to the proper and reproducible activation of muscle gene expression, the role and mode of function of other MRFs still remains largely unclear. Recent in vivo findings using the Xenopus embryo model strongly support the concept that a single MRF can specifically control a subset of muscle genes and, thus, can be substituted by other MRFs albeit with dramatically lower efficiency. The topic of this review is to summarize the molecular data accounting for a redundant and/or specific involvement of each member of the MyoD family in myogenesis in the light of recent studies on the Xenopus model.