Molecular and Cellular Regulation of Skeletal Myogenesis

Since the seminal discovery of the cell-fate regulator Myod, studies in skeletal myogenesis have inspired the search for cell-fate regulators of similar potential in other tissues and organs. It was perplexing that a similar transcription factor for other tissues was not found; however, it was later discovered that combinations of molecular regulators can divert somatic cell fates to other cell types. With the new era of reprogramming to induce pluripotent cells, the myogenesis paradigm can now be viewed under a different light. Here, we provide a short historical perspective and focus on how the regulation of skeletal myogenesis occurs distinctly in different scenarios and anatomical locations. In addition, some interesting features of this tissue underscore the importance of reconsidering the simple-minded view that a single stem cell population emerges after gastrulation to assure tissuegenesis. Notably, a self-renewing long-term Pax7+ myogenic stem cell population emerges during development only after a first wave of terminal differentiation occurs to establish a tissue anlagen in the mouse. How the future stem cell population is selected in this unusual scenario will be discussed. Recently, a wealth of information has emerged from epigenetic and genome-wide studies in myogenic cells. Although key transcription factors such as Pax3, Pax7, and Myod regulate only a small subset of genes, in some cases their genomic distribution and binding are considerably more promiscuous. This apparent nonspecificity can be reconciled in part by the permissivity of the cell for myogenic commitment, and also by new roles for some of these regulators as pioneer transcription factors acting on chromatin state.