Neogenin Regulation of BMP-Induced Canonical Smad Signaling and Endochondral Bone Formation

Zheng Zhou, Jianxin Xie, Daehoon Lee, Yu Liu, Jiung Jung, Lijuan Zhou, Shan Xiong, Lin Mei, Wencheng Xiong

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Neogenin has been identified as a receptor for the neuronal axon guidance cues netrins and RGMs (repulsive guidance molecules). Here we provide evidence for neogenin in regulating endochondral bone development and BMP (bone morphogenetic protein) signaling. Neogenin-deficient mice were impaired in digit/limb development and endochondral ossification. BMP2 induction of Smad1/5/8 phosphorylation and Runx2 expression, but not noncanonical p38 MAPK activation, was reduced in chondrocytes from neogenin mutant mice. BMP receptor association with membrane microdomains, which is necessary for BMP signaling to Smad, but not p38 MAPK, was diminished in neogenin-deficient chondrocytes. Furthermore, RGMs appear to mediate neogenin interaction with BMP receptors in chondrocytes. Taken together, our results indicate that neogenin promotes chondrogenesis in vitro and in vivo, revealing an unexpected mechanism underlying neogenin regulation of BMP signaling.

Original languageEnglish (US)
Pages (from-to)90-102
Number of pages13
JournalDevelopmental Cell
Volume19
Issue number1
DOIs
StatePublished - Jul 1 2010

Keywords

  • Devio
  • Signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Zhou, Z., Xie, J., Lee, D., Liu, Y., Jung, J., Zhou, L., Xiong, S., Mei, L., & Xiong, W. (2010). Neogenin Regulation of BMP-Induced Canonical Smad Signaling and Endochondral Bone Formation. Developmental Cell, 19(1), 90-102. https://doi.org/10.1016/j.devcel.2010.06.016