Regulators of Cartilage Formation

先前的研究表明来自脊索和底板的Shh赋予体细胞经历BMP软骨形成的能力。基于该模型，我们认为Shh诱导了一种能力因子的表达，该能力因子与bmp协同促进软骨分化。我们已经描述了两种转录因子作为这样的能力因子。在Shh缺失的情况下，Sox9和Nkx3.2都能促进软骨的形成。它们相互诱导表达，形成正调控循环。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是一种转录抑制因子，我将通过底物杂交分析确定可能被Nkx3.2抑制的软骨抑制剂。我相信，我的研究将导致更好地了解软骨形成的机制，这可能在未来的临床有用。

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.