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Originally published In Press as doi:10.1074/jbc.M708594200 on December 3, 2007
J. Biol. Chem., Vol. 283, Issue 6, 3529-3536, February 8, 2008
Smarcd3 Regulates the Timing of Zebrafish Myogenesis Onset*
Haruki Ochi,
Stefan Hans1, and
Monte Westerfield2
From the
Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403-1254
A cascade of signaling events triggers myogenesis in vertebrates. Although studies of zebrafish indicate that fibroblast growth factor (Fgf), Hedgehog (Hh), and the T-box transcription factors, No tail (Ntl) and T-box gene 16 (Tbx16), regulate myogenesis, the hierarchy of these factors has not been determined. Recently, another transcriptional cofactor, Smarcd3, a subunit of the SWI/SNF chromatin-remodeling complex, has been shown to be required for heart muscle formation in mouse. In zebrafish, fgf8 and ntl expression commences during blastula stages, whereas myogenesis, as indicated by myod expression, does not begin until much later during mid-gastrula stages. smarcd3b expression, on the other hand, becomes enriched in the marginal zone just prior to the beginning of myod expression. Overexpression of smarcd3 shifts the onset of myod and myf5 expression earlier, and myod and myf5 expression in adaxial cells, the earliest muscle precursors, requires Smarcd3, indicating that Smarcd3 is the limiting factor that regulates the onset of myogenesis. Smarcd3 physically interacts with Ntl, and Smarcd3 overexpression fails to rescue myod expression in ntl mutants, demonstrating that function of Smarcd3 depends on Ntl activity. We propose a model in which cooperative activity of Fgf, Ntl, and Smarcd3 is required for the onset of myogenesis, with Smarcd3b serving as the primary regulator of the timing of myogenesis onset.
Received for publication, October 16, 2007
, and in revised form, November 9, 2007.
* This work was supported by National Institutes of Health Grants AR45575 and HD22486. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2 and Table S1.
1 Current address: Biotechnology Center and Center of Regenerative Therapies, University of Technology, Dresden, Germany.
2 To whom correspondence should be addressed: Institute of Neuroscience, University of Oregon, Eugene, OR 97403-1254. E-mail: monte{at}uoneuro.uoregon.edu.

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Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.
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