Youngwoo Kim

Publications (2)9.66 Total impact

• Article: 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, Haruhiko Akiyama
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  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.
  Nature Communications 03/2011; 2:251. · 7.40 Impact Factor
• Article: Generation of transgenic mice for conditional overexpression of Sox9.

  Youngwoo Kim, Hiroki Murao, Koji Yamamoto, Jian Min Deng, Richard R Behringer, Takashi Nakamura, Haruhiko Akiyama
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  ABSTRACT: Sox9 belongs to the family of Sry-related high-mobility group box transcription factors controlling cell fate, cell proliferation and differentiation in various tissues, including cartilage, testis, the central nervous system, kidney, and gastrointestine. Mice conditionally lacking Sox9 have revealed essential roles for Sox9 in these tissues. To gain further insight into the role of Sox9 in different tissues and at different stages of development, we have generated a transgenic mouse line to express Sox9 in a Cre recombinase-dependent manner. The construct contained the human cytomegalovirus enhancer and chicken β-actin promoter, and a floxed monomeric red fluorescence protein 1 (mRFP1) cassette to direct ubiquitous expression of mRFP1. Cre expression removed the mRFP1 gene, allowing expression of Sox9 and enhanced green fluorescent protein. Expectedly, overexpression of Sox9 in chondrocytes using Col2a1-Cre mice suppressed chondrocyte hypertrophy, and delayed terminal differentiation and subsequent ossification. Misexpression of Sox9 in hypertrophic chondrocytes using Col10a1-Cre knock-in mice also delayed terminal differentiation. This Sox9 conditional transgenic mouse line will be a valuable tool to uncover tissue-specific and developmental stage-specific functions of Sox9.
  Journal of Bone and Mineral Metabolism 01/2011; 29(1):123-9. · 2.27 Impact Factor