Regulators of Cartilage Formation

以前的工作表明，来自脊索和底板的Shh赋予体节细胞进行BMP软骨形成的能力。基于该模型，提出Shh诱导与BMP协同促进软骨分化的感受态因子的表达。我们已经确定了两个转录因子作为这种感受态因子。Sox 9和Nkx3.2两者在Shh不存在的情况下促进软骨形成。此外，它们诱导彼此的表达以建立正调控环。我建议调查，如果Sox 9所需的Nkx3.2诱导软骨形成利用Sox 9-En，Nkx3.2的显性负性形式。由于Nkx3.2的功能作为一个转录抑制因子，我将确定潜在的软骨抑制剂，抑制Nkx3.2通过底物杂交分析。我相信，我的研究将导致更好地了解软骨形成的机制，这可能是临床有用的未来。

Previous work has indicated that Shh from notochord and floor plate confers the competence to somitic cells to undergo BMP cartilage formation. Based on this model, it was suggested that Shh induces the expression of a competence factor(s) which cooperates with BMPs to promote cartilage differentiation. We have characterized two transcription factors as such competence factors. Both Sox9 and Nkx3.2 promote cartilage formation in the absence of Shh. Furthermore, they induce each other's expression to establish a positive regulatory loop. I propose to investigate if Sox9 is required for Nkx3.2 induced chondrogenesis by utilizing Sox9-En, a dominant negative form of Nkx3.2. Since Nkx3.2 functions as a transcription repressor, I will identify potential cartilage inhibitors that are repressed by Nkx3.2 through substrate hybridization analysis. I am confident that my research will lead to a better understanding of the mechanism of cartilage formation, which may be clinical useful in the future.