Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development
- PMID: 16141219
- DOI: 10.1242/dev.02025
Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development
Abstract
Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development, including proliferation and maturation of chondrocytes, osteoblast development and cartilage vascularization. Although it is known that Gli transcription factors are key effectors of hedgehog signaling, it has not been established which Gli protein mediates Ihh activity in skeletal development. Here, we show that removal of Gli3 in Ihh-null mouse embryos restored normal proliferation and maturation of chondrocytes, but only partially rescued the defects in osteoblast development and cartilage vascularization. Remarkably, in both Ihh-/- and Ihh-/-; Gli3-/- embryos, vascularization promoted osteoblast development in perichondrial progenitor cells. Our results not only establish Gli3 as a critical effector for Ihh activity in the developing skeleton, but also identify an osteogenic role for a vasculature-derived signal, which integrates with Ihh and Wnt signals to determine the osteoblast versus chondrocyte fate in the mesenchymal progenitors.
Similar articles
-
Indian hedgehog synchronizes skeletal angiogenesis and perichondrial maturation with cartilage development.Development. 2005 Mar;132(5):1057-67. doi: 10.1242/dev.01649. Epub 2005 Feb 2. Development. 2005. PMID: 15689378
-
Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton.Development. 2004 Mar;131(6):1309-18. doi: 10.1242/dev.01006. Epub 2004 Feb 18. Development. 2004. PMID: 14973297
-
Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors.Development. 2006 Aug;133(16):3231-44. doi: 10.1242/dev.02480. Epub 2006 Jul 19. Development. 2006. PMID: 16854976
-
Indian hedgehog: its roles and regulation in endochondral bone development.J Cell Biochem. 2005 Dec 15;96(6):1163-73. doi: 10.1002/jcb.20635. J Cell Biochem. 2005. PMID: 16187314 Review.
-
Signaling networks in RUNX2-dependent bone development.J Cell Biochem. 2011 Mar;112(3):750-5. doi: 10.1002/jcb.22994. J Cell Biochem. 2011. PMID: 21328448 Review.
Cited by
-
Overexpression of Smurf2 stimulates endochondral ossification through upregulation of beta-catenin.J Bone Miner Res. 2008 Apr;23(4):552-63. doi: 10.1359/jbmr.071115. J Bone Miner Res. 2008. PMID: 18052755 Free PMC article.
-
Combined Transcriptomics and Metabolomics Identify Regulatory Mechanisms of Porcine Vertebral Chondrocyte Development In Vitro.Int J Mol Sci. 2024 Jan 18;25(2):1189. doi: 10.3390/ijms25021189. Int J Mol Sci. 2024. PMID: 38256262 Free PMC article.
-
Indian Hedgehog signalling triggers Nkx3.2 protein degradation during chondrocyte maturation.Biochem J. 2012 May 1;443(3):789-98. doi: 10.1042/BJ20112062. Biochem J. 2012. PMID: 22507129 Free PMC article.
-
Signaling pathways regulating the specification and differentiation of the osteoblast lineage.Regen Ther. 2015 Jan 28;1:57-62. doi: 10.1016/j.reth.2014.10.002. eCollection 2015 Jun. Regen Ther. 2015. PMID: 31245441 Free PMC article. Review.
-
Proximal tibial osteochondromas in patients with fibrodysplasia ossificans progressiva.J Bone Joint Surg Am. 2008 Feb;90(2):366-74. doi: 10.2106/JBJS.G.00774. J Bone Joint Surg Am. 2008. PMID: 18245597 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources