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Publication : Neogenin regulation of BMP-induced canonical Smad signaling and endochondral bone formation.

First Author  Zhou Z Year  2010
Journal  Dev Cell Volume  19
Issue  1 Pages  90-102
PubMed ID  20643353 Mgi Jnum  J:162626
Mgi Id  MGI:4819431 Doi  10.1016/j.devcel.2010.06.016
Citation  Zhou Z, et al. (2010) Neogenin regulation of BMP-induced canonical Smad signaling and endochondral bone formation. Dev Cell 19(1):90-102
abstractText  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.
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