Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development
Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development
复制标题
DOI：
10.1242/dev.02025
复制
发表时间：
2005-10-01
期刊：
影响因子：
4.6
通讯作者：
Long, FX
中科院分区：
文献类型：
--
作者：
Hilton, MJ;Tu, XL;Long, FX
印度刺猬(IHH)控制软骨内骨骼发育的多个方面，包括软骨细胞的增殖和成熟、成骨细胞的发育和软骨血管的形成。虽然已知Gli转录因子是Hedgehog信号转导的关键效应者，但Gli蛋白在骨骼发育过程中介导IHH活性的机制尚不清楚。在这里，我们表明，在IHH缺失的小鼠胚胎中去除Gli3恢复了软骨细胞的正常增殖和成熟，但仅部分修复了成骨细胞发育和软骨血管形成的缺陷。值得注意的是，在IHH(-/-)和IHH(-/-)；Gli(3-/-)胚胎中，血管化促进了软骨膜前体细胞的成骨细胞发育。我们的结果不仅证实了Gli3在发育中的骨骼中是IHH活性的关键效应因子，而且还确定了血管衍生信号的成骨作用，该信号与IHH和Wnt信号相结合，决定了间充质祖细胞中成骨细胞与软骨细胞的命运。
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(-/-); Gli(3-/-) 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.