Hedgehog signaling activates a positive feedback mechanism involving insulin-like growth factors to induce osteoblast differentiation.


Journal Article

Hedgehog (Hh) signaling is essential for osteoblast differentiation in the endochondral skeleton during embryogenesis. However, the molecular mechanism underlying the osteoblastogenic role of Hh is not completely understood. Here, we report that Hh markedly induces the expression of insulin-like growth factor 2 (Igf2) that activates the mTORC2-Akt signaling cascade during osteoblast differentiation. Igf2-Akt signaling, in turn, stabilizes full-length Gli2 through Serine 230, thus enhancing the output of transcriptional activation by Hh. Importantly, genetic deletion of the Igf signaling receptor Igf1r specifically in Hh-responding cells diminishes bone formation in the mouse embryo. Thus, Hh engages Igf signaling in a positive feedback mechanism to activate the osteogenic program.

Full Text

Duke Authors

Cited Authors

  • Shi, Y; Chen, J; Karner, CM; Long, F

Published Date

  • April 14, 2015

Published In

Volume / Issue

  • 112 / 15

Start / End Page

  • 4678 - 4683

PubMed ID

  • 25825734

Pubmed Central ID

  • 25825734

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1502301112


  • eng

Conference Location

  • United States