Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25

Yukio Nakamura, Koji Yamamoto, Xinjun He, Bungo Otsuki, Youngwoo Kim, Hiroki Murao, Tsunemitsu Soeda, Noriyuki Tsumaki, Jian Min Deng, Zhaoping Zhang, Richard R. Behringer, Benoit de Crombrugghe, John H. Postlethwait, Matthew L. Warman, Takashi Nakamura and Haruhiko Akiyama ()
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Yukio Nakamura: Clinical Research Center, Murayama Medical Center
Koji Yamamoto: Kyoto University
Xinjun He: Institute of Neuroscience, University of Oregon
Bungo Otsuki: Kyoto University
Youngwoo Kim: Kyoto University
Hiroki Murao: Kyoto University
Tsunemitsu Soeda: Kyoto University
Noriyuki Tsumaki: Osaka University
Jian Min Deng: The University of Texas M.D. Anderson Cancer Center
Zhaoping Zhang: The University of Texas M.D. Anderson Cancer Center
Richard R. Behringer: The University of Texas M.D. Anderson Cancer Center
Benoit de Crombrugghe: The University of Texas M.D. Anderson Cancer Center
John H. Postlethwait: Institute of Neuroscience, University of Oregon
Matthew L. Warman: Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School
Takashi Nakamura: Kyoto University
Haruhiko Akiyama: Kyoto University

Nature Communications, 2011, vol. 2, issue 1, 1-10

Abstract: Abstract Sox9 is a direct transcriptional activator of cartilage-specific extracellular matrix genes and has essential roles in chondrogenesis. Mutations in or around the SOX9 gene cause campomelic dysplasia or Pierre Robin Sequence. However, Sox9-dependent transcriptional control in chondrogenesis remains largely unknown. Here we identify Wwp2 as a direct target of Sox9. Wwp2 interacts physically with Sox9 and is associated with Sox9 transcriptional activity via its nuclear translocation. A yeast two-hybrid screen using a cDNA library reveals that Wwp2 interacts with Med25, a component of the Mediator complex. The positive regulation of Sox9 transcriptional activity by Wwp2 is mediated by the binding between Sox9 and Med25. In zebrafish, morpholino-mediated knockdown of either wwp2 or med25 induces palatal malformation, which is comparable to that in sox9 mutants. These results provide evidence that the regulatory interaction between Sox9, Wwp2 and Med25 defines the Sox9 transcriptional mechanisms of chondrogenesis in the forming palate.

Date: 2011
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DOI: 10.1038/ncomms1242

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