Regulators of Cartilage Formation

以前的工作表明，脊索和底板中的Shh赋予体细胞进行BMP软骨形成的能力。根据这一模型，推测Shh诱导一种能力因子(S)的表达，该因子与BMPs协同促进软骨分化。我们已经将两种转录因子定性为这种能力因子。在没有Shh的情况下，Sox9和Nkx3.2都促进软骨的形成。此外，它们还会诱导彼此的表达，从而建立一个正向调控环。我建议利用Nkx3.2的显性阴性形式Sox9-en来研究Nkx3.2诱导的软骨形成是否需要Sox9。由于Nkx3.2作为转录抑制因子发挥作用，我将通过底物杂交分析来确定Nkx3.2抑制的潜在软骨抑制因子。我相信，我的研究将有助于更好地了解软骨形成的机制，这可能在未来的临床上有用。

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.