Hsu Shu-Hsuan Claire, Noamani Babak, Abernethy Danielle E, Zhu Hui, Levi Giovanni, Bendall Andrew J
Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ont., Canada N1G 2W1.
Mech Dev. 2006 Nov;123(11):819-30. doi: 10.1016/j.mod.2006.08.005. Epub 2006 Aug 22.
During endochondral ossification in the vertebrate limb, multipotent mesenchymal cells first differentiate into chondroblasts (chondrogenesis) that further differentiate (via chondrocyte hypertrophy) to a terminal cellular phenotype. Dlx5 and Dlx6 are functionally redundant regulators of chondrocyte hypertrophy. We now show that Dlx5 and Dlx6 also regulate the earlier step of chondrogenesis in the limb. Limb bud mesenchymal cells from Dlx5/6(-/-) embryos show reduced chondrogenesis compared to wild-type littermates, and expression of either Dlx5 or Dlx6 stimulated differentiation of limb bud mesenchymal cells to chondroblasts. The functional overlap between Dlx5 and Dlx6 occurs despite the fact that the amino- and carboxyl-terminal domains of the encoded proteins are dissimilar. In order to reconcile the disparity between the divergent structures of Dlx5 and Dlx6 with their overlapping biological functions, we investigated the domain requirements and transcriptional activities associated with Dlx5- and Dlx6-mediated chondrogenesis. We find distinct domain requirements for the chondrogenic function of these related homeoproteins, indicating divergent molecular mechanisms of action.
在脊椎动物肢体的软骨内成骨过程中，多能间充质细胞首先分化为成软骨细胞（软骨形成），成软骨细胞进一步分化（通过软骨细胞肥大）为终末细胞表型。Dlx5和Dlx6是软骨细胞肥大的功能冗余调节因子。我们现在表明，Dlx5和Dlx6也调节肢体软骨形成的早期步骤。与野生型同窝仔相比，来自Dlx5/6(-/-)胚胎的肢芽间充质细胞显示软骨形成减少，并且Dlx5或Dlx6的表达刺激肢芽间充质细胞向成软骨细胞分化。尽管编码蛋白的氨基末端和羧基末端结构域不同，但Dlx5和Dlx6之间仍存在功能重叠。为了协调Dlx5和Dlx6不同结构与其重叠生物学功能之间的差异，我们研究了与Dlx5和Dlx6介导的软骨形成相关的结构域要求和转录活性。我们发现这些相关同源蛋白的软骨形成功能有不同的结构域要求，表明其作用的分子机制不同。
