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Published online December 3, 2007
doi:10.1083/jcb.200709083
The Journal of Cell Biology, Vol. 179, No. 5, 911-922
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Holterman et al.
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Article

Megf10 regulates the progression of the satellite cell myogenic program

Chet E. Holterman1,2, Fabien Le Grand2, Shihuan Kuang2, Patrick Seale3, and Michael A. Rudnicki1,2,3

1 Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada K1N 6N5
2 The Sprott Center for Stem Cell Research, Ottawa Health Research Institute Regenerative Medicine Program, Ottawa, Canada K1H 8L6
3 Department of Biology, McMaster University, Hamilton, Canada L8S 4K1

Correspondence to Michael A. Rudnicki: mrudnicki{at}ohri.ca

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.

C.E. Holterman and F. Le Grand contributed equally to this paper.

Abbreviations used in this paper: DIG, digoxigenin; EDL, extensor digitorum longus; GAPDH, glyceraldehyde 3–phosphate dehydrogenase; MyHC, myosin heavy chain; RDA, representational difference analysis; shRNA, short hairpin RNA.


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