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Kif7 promotes hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu.

Publication ,  Journal Article
Hsu, S-HC; Zhang, X; Yu, C; Li, ZJ; Wunder, JS; Hui, C-C; Alman, BA
Published in: Development
September 2011

Proper regulation of Indian hedgehog (Ihh) signaling is vital for chondrocyte proliferation and differentiation in the growth plate. Its dysregulation causes skeletal dysplasia, osteoarthritis or cartilaginous neoplasia. Here, we show that Suppressor of fused (Sufu) and Kif7 are essential regulators of Ihh signaling. While Sufu acts as a negative regulator of Gli transcription factors, Kif7 functions both positively and negatively in chondrocytes. Kif7 plays a role in the turnover of Sufu and the exclusion of Sufu-Gli complexes from the primary cilium. Importantly, halving the dose of Sufu restores normal hedgehog pathway activity and chondrocyte development in Kif7-null mice, demonstrating that the positive role of Kif7 is to restrict the inhibitory activity of Sufu. Furthermore, Kif7 also inhibits Gli transcriptional activity in the chondrocytes when Sufu function is absent. Therefore, Kif7 regulates the activity of Gli transcription factors through both Sufu-dependent and -independent mechanisms.

Duke Scholars

Published In

Development

DOI

EISSN

1477-9129

Publication Date

September 2011

Volume

138

Issue

17

Start / End Page

3791 / 3801

Location

England

Related Subject Headings

  • Signal Transduction
  • Repressor Proteins
  • Polymerase Chain Reaction
  • Mice
  • Kinesins
  • In Situ Hybridization
  • Immunoprecipitation
  • Immunohistochemistry
  • Hedgehog Proteins
  • Growth Plate
 

Citation

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Hsu, S.-H., Zhang, X., Yu, C., Li, Z. J., Wunder, J. S., Hui, C.-C., & Alman, B. A. (2011). Kif7 promotes hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu. Development, 138(17), 3791–3801. https://doi.org/10.1242/dev.069492
Hsu, Shu-Hsuan C., Xiaoyun Zhang, Chunying Yu, Zhu Juan Li, Jay S. Wunder, Chi-Chung Hui, and Benjamin A. Alman. “Kif7 promotes hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu.Development 138, no. 17 (September 2011): 3791–3801. https://doi.org/10.1242/dev.069492.
Hsu S-HC, Zhang X, Yu C, Li ZJ, Wunder JS, Hui C-C, et al. Kif7 promotes hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu. Development. 2011 Sep;138(17):3791–801.
Hsu, Shu-Hsuan C., et al. “Kif7 promotes hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu.Development, vol. 138, no. 17, Sept. 2011, pp. 3791–801. Pubmed, doi:10.1242/dev.069492.
Hsu S-HC, Zhang X, Yu C, Li ZJ, Wunder JS, Hui C-C, Alman BA. Kif7 promotes hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu. Development. 2011 Sep;138(17):3791–3801.
Journal cover image

Published In

Development

DOI

EISSN

1477-9129

Publication Date

September 2011

Volume

138

Issue

17

Start / End Page

3791 / 3801

Location

England

Related Subject Headings

  • Signal Transduction
  • Repressor Proteins
  • Polymerase Chain Reaction
  • Mice
  • Kinesins
  • In Situ Hybridization
  • Immunoprecipitation
  • Immunohistochemistry
  • Hedgehog Proteins
  • Growth Plate