Myostatin signals through Pax7 to regulate satellite cell self-renewal

Journal Article · Tue Jan 15 00:00:00 EST 2008 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2007.09.012· OSTI ID:21045928

McFarlane, Craig ^[1]; Hennebry, Alex; Thomas, Mark; Plummer, Erin ^[1]; Ling, Nicholas ^[2]; Sharma, Mridula ^[1]; Kambadur, Ravi ^[1]

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1. AgResearch, Functional Muscle Genomics, Hamilton (New Zealand)
2. Department of Biological Sciences, University of Waikato, Hamilton (New Zealand)

Myostatin, a Transforming Growth Factor-beta (TGF-{beta}) super-family member, has previously been shown to negatively regulate satellite cell activation and self-renewal. However, to date the mechanism behind Myostatin function in satellite cell biology is not known. Here we show that Myostatin signals via a Pax7-dependent mechanism to regulate satellite cell self-renewal. While excess Myostatin inhibited Pax7 expression via ERK1/2 signaling, an increase in Pax7 expression was observed following both genetic inactivation and functional antagonism of Myostatin. As a result, we show that either blocking or inactivating Myostatin enhances the partitioning of the fusion-incompetent self-renewed satellite cell lineage (high Pax7 expression, low MyoD expression) from the pool of actively proliferating myogenic precursor cells. Consistent with this result, over-expression of Pax7 in C2C12 myogenic cells resulted in increased self-renewal through a mechanism which slowed both myogenic proliferation and differentiation. Taken together, these results suggest that increased expression of Pax7 promotes satellite cell self-renewal, and furthermore Myostatin may control the process of satellite cell self-renewal through regulation of Pax7. Thus we speculate that, in addition to the intrinsic factors (such as Pax7), extrinsic factors both positive and negative in nature, will play a major role in determining the stemness of skeletal muscle satellite cells.

• OSTI ID: 21045928
• Journal Information: Experimental Cell Research, Vol. 314, Issue 2; Other Information: DOI: 10.1016/j.yexcr.2007.09.012; PII: S0014-4827(07)00443-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
GENE REGULATION
GROWTH FACTORS
INTRINSIC FACTOR
MUSCLES