Skeletal muscles contain an undifferentiated myogenic stem cell pool (satellite cells) that can be mobilized to regenerate myofibers in response to injury. We have determined that the winged helix transcription factor MNF is expressed selectively in quiescent satellite cells, which do not express known regulators of the myogenic program. Following muscle injury, MNF is present transiently in proliferating satellite cells and in centralized nuclei of regenerating myofibers, but expression declines as these fibers mature, until only the residual stem cell pool continues to express detectable levels of MNF. MNF also is expressed selectively but transiently at embryonic stages of myogenesis in the developing myotome, limb bud precursors, and heart tube, but by late fetal stages of development, MNF is down-regulated within differentiated cardiac and skeletal myocytes, and persistently high expression is observed only in satellite cells. These data identify MNF as a marker of quiescent satellite cells and suggest that downstream genes controlled by MNF serve to modulate proliferative growth or differentiation in this unique cell population.
Bibliographical noteFunding Information:
This work was supported by Public Health Service Grant RO1 AR40849 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and by American Heart Association Grant-in-Aid 95G-112. D.J.G. is a recipient of Clinical Investigator Development Award HL03231 from the National Heart, Lung, and Blood Institute. The authors acknowledge the generosity of E. N. Olson, A. Rawls, and M. Rudnicki, as they provided homozygous null mutant embryos. We also thank E. N. Olson, W. Wright, M. Siegelman, E. Fernandez, and S. Konieczny for antisera used in this study. J. Shelton is acknowledged for his assistance with the preparation of the photographic prints that appear in this paper and D. Belloto for his assistance with the ultrastructural immunolocali-zation studies.