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First published online 15 August 2007
doi: 10.1242/dev.003905

Development 134, 3371-3382 (2007)
Published by The Company of Biologists 2007
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Pbx homeodomain proteins direct Myod activity to promote fast-muscle differentiation

Lisa Maves1,*, Andrew Jan Waskiewicz2, Biswajit Paul1, Yi Cao1, Ashlee Tyler1, Cecilia B. Moens3 and Stephen J. Tapscott1

1 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
2 Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G2E9, Canada.
3 Howard Hughes Medical Institute and Division of Basic Science, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

* Author for correspondence (e-mail: lmaves{at}fhcrc.org)

Accepted 13 July 2007

The basic helix-loop-helix (bHLH) transcription factor Myod directly regulates gene expression throughout the program of skeletal muscle differentiation. It is not known how a Myod-driven myogenic program is modulated to achieve muscle fiber-type-specific gene expression. Pbx homeodomain proteins mark promoters of a subset of Myod target genes, including myogenin (Myog); thus, Pbx proteins might modulate the program of myogenesis driven by Myod. By inhibiting Pbx function in zebrafish embryos, we show that Pbx proteins are required in order for Myod to induce the expression of a subset of muscle genes in the somites. In the absence of Pbx function, expression of myog and of fast-muscle genes is inhibited, whereas slow-muscle gene expression appears normal. By knocking down Pbx or Myod function in combination with another bHLH myogenic factor, Myf5, we show that Pbx is required for Myod to regulate fast-muscle, but not slow-muscle, development. Furthermore, we show that Sonic hedgehog requires Myod in order to induce both fast- and slow-muscle markers but requires Pbx only to induce fast-muscle markers. Our results reveal that Pbx proteins modulate Myod activity to drive fast-muscle gene expression, thus showing that homeodomain proteins can direct bHLH proteins to establish a specific cell-type identity.

Key words: Myod, Pbx, Muscle, Zebrafish






© The Company of Biologists Ltd 2007