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J. Cell Biol., Volume 142, Number 2, July 27, 1998 537-544

Bcl-2 Expression Identifies an Early Stage of Myogenesis and Promotes Clonal Expansion of Muscle Cells

Janice A. Dominov,*Dagger Jonathan J. Dunn,* and Jeffrey Boone Miller*Dagger

* Myogenesis Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129; and Dagger  Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115

We show that Bcl-2 expression in skeletal muscle cells identifies an early stage of the myogenic pathway, inhibits apoptosis, and promotes clonal expansion. Bcl-2 expression was limited to a small proportion of the mononucleate cells in muscle cell cultures, ranging from ~1-4% of neonatal and adult mouse muscle cells to ~5-15% of the cells from the C2C12 muscle cell line. In rapidly growing cultures, some of the Bcl-2-positive cells coexpressed markers of early stages of myogenesis, including desmin, MyoD, and Myf-5. In contrast, Bcl-2 was not expressed in multinucleate myotubes or in those mononucleate myoblasts that expressed markers of middle or late stages of myogenesis, such as myogenin, muscle regulatory factor 4 (MRF4), and myosin. The small subset of Bcl-2-positive C2C12 cells appeared to resist staurosporine-induced apoptosis. Furthermore, though myogenic cells from genetically Bcl-2-null mice formed myotubes normally, the muscle colonies produced by cloned Bcl-2-null cells contained only about half as many cells as the colonies produced by cells from wild-type mice. This result suggests that, during clonal expansion from a muscle progenitor cell, the number of progeny obtained is greater when Bcl-2 is expressed.

Key words: apoptosisBcl-2myoblastmyogeninskeletal muscle


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