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J. Cell Biol.,
Volume 142, Number 6, September 21, 1998 1447-1459
* Cell Biology Unit, Institut de Génétique Humaine, Unité Propre de Recherche 1142, Centre National de la Recherche
Scientifique, 34396 Montpellier Cedex 5, France; and The muscle regulators MyoD and Myf-5 control cell cycle withdrawal and induction of differentiation in skeletal muscle cells. By immunofluorescence
analysis, we show that MyoD and Myf-5 expression patterns become mutually exclusive when C2 cells are induced to differentiate with Myf-5 staining present in
cells which fail to differentiate. Isolation of these undifferentiated cells reveals that upon serum stimulation
they reenter the cell cycle, express MyoD and downregulate Myf-5. Similar regulations of MyoD and Myf-5 were observed using cultured primary myoblasts derived from satellite cells. To further analyze these regulations of MyoD and Myf-5 expression, we synchronized proliferating myoblasts. Analysis of MyoD and
Myf-5 expression during cell cycle progression revealed distinct and contrasting profiles of expression. MyoD is
absent in G0, peaks in mid-G1, falls to its minimum
level at G1/S and reaugments from S to M. In contrast,
Myf-5 protein is high in G0, decreases during G1 and
reappears at the end of G1 to remain stable until mitosis. These data demonstrate that the two myogenic factors MyoD and Myf-5 undergo specific and distinct cell
cycle-dependent regulation, thus establishing a correlation between the cell cycle-specific ratios of MyoD and
Myf-5 and the capacity of cells to differentiate: (a) in
G1, when cells express high levels of MyoD and enter
differentiation; (b) in G0, when cells express high levels
of Myf-5 and fail to differentiate.
Institut Pasteur, Department de Biologie Moleculaire, 75724 Paris Cedex
15, France
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