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

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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

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Bone Morphogenetic Proteins
Osteogenesis
Bone
Chondrocytes
Bone Morphogenetic Protein Receptors
p38 Mitogen-Activated Protein Kinases
Membrane Microdomains
Chondrogenesis
Phosphorylation
Molecules
neogenin
Bone Development
Cues
Extremities
Chemical activation
Association reactions
Membranes
Bone and Bones

Keywords

  • Devio
  • Signaling

ASJC Scopus subject areas

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

Cite this

Neogenin Regulation of BMP-Induced Canonical Smad Signaling and Endochondral Bone Formation. / Zhou, Zheng; Xie, Jianxin; Lee, Daehoon; Liu, Yu; Jung, Jiung; Zhou, Lijuan; Xiong, Shan; Mei, Lin; Xiong, Wencheng.

In: Developmental Cell, Vol. 19, No. 1, 01.07.2010, p. 90-102.

Research output: Contribution to journalArticle

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, vol. 19, no. 1, pp. 90-102. https://doi.org/10.1016/j.devcel.2010.06.016
Zhou, Zheng ; Xie, Jianxin ; Lee, Daehoon ; Liu, Yu ; Jung, Jiung ; Zhou, Lijuan ; Xiong, Shan ; Mei, Lin ; Xiong, Wencheng. / Neogenin Regulation of BMP-Induced Canonical Smad Signaling and Endochondral Bone Formation. In: Developmental Cell. 2010 ; Vol. 19, No. 1. pp. 90-102.
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