Megf10 regulates the progression of the satellite cell myogenic program.
We identify here the multiple epidermal growth factor repeat transmembrane protein Megf10 as a quiescent satellite cell marker that is also expressed in skeletal myoblasts but not in differentiated myofibers. Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation. Infected myoblasts that fail to differentiate undergo cell cycle arrest and can reenter the cell cycle upon serum restimulation. Moreover, experimental modulations of Megf10 alter the expression levels of Pax7 and the myogenic regulatory factors. In contrast, Megf10 silencing in activated satellite cells on individual fibers or in cultured myoblasts results in a dramatic reduction in the cell number, caused by myogenin activation and precocious differentiation as well as a depletion of the self-renewing Pax7+/MyoD- population. Additionally, Megf10 silencing in MyoD-/- myoblasts results in down-regulation of Notch signaling components. We conclude that Megf10 represents a novel transmembrane protein that impinges on Notch signaling to regulate the satellite cell population balance between proliferation and differentiation.
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada K1N 6N5.
Chet E
CE
Holterman
Fabien
F
Le Grand
Shihuan
S
Kuang
Patrick
P
Seale
Michael A
MA
Rudnicki
D000818:Animals; D002451:Cell Compartmentation; D002454:Cell Differentiation; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000302:isolation & purification; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*; D044967:Serum; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D018076:DNA, Complementary; C525222:Megf10 protein, mouse; D008565:Membrane Proteins; D051880:Receptors, Notch