Article

Megf10 regulates the progression of the satellite cell myogenic program

Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada K1N 6N5.
The Journal of Cell Biology (Impact Factor: 9.69). 01/2008; 179(5):911-22. DOI: 10.1083/jcb.200709083
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ABSTRACT 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.

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Available from: Chet E Holterman, Aug 23, 2015
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    • "Recessive mutations in MEGF10 (MIM 612453) were associated with early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD; MIM 614399) (Logan et al., 2011; Boyden et al., 2012). MEGF10 is expressed in quiescent and activated satellite cells and knock-down of Megf10 in mouse muscle resulted in satellite cell depletion (Holterman et al., 2007). EMARDD patient muscle showed reduced mean myofibre diameter and lacked PAX7 + nuclei (Logan et al., 2011). "
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    • "RBP-J QSC, ASC Co-activator of notch signaling Maintain satellite cell number Bjornson et al., 2012; Mourikis et al., 2012 MEGF10 QSC, ASC Activate Notch signaling Maintain satellite cell number Holterman et al., 2007 Collagen VI ECM for QSC Increased muscle stiffness Maintain satellite cell self- renewal Urciuolo et al., 2013 Hypoxia Outside of QSC Down-regulate miR-1/206 Surpresse MyoD expression Maintain satellite cell in quiescent state Liu et al., 2012 QSC, quiescent satellite cells; ASC, activated satellite cells; RC, reserve cells; ECM, extracelllular matrix. "
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    • "Satellite cells were found to be depleted in the skeletal muscle tissue of a MEGF10 myopathy patient [2]. Concordantly, it was reported that MEGF10 overexpression in C2C12 myoblasts enhances cell proliferation and that knockdown of MEGF10 in muscle fibers leads to a reduction of satellite cells due to premature differentiation [4]. MEGF10 is also highly expressed in the central nervous system [5]. "
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