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.
| Zeng, Li; Kempf, Herve; Murtaugh, L Charles et al. (2002) Shh establishes an Nkx3.2/Sox9 autoregulatory loop that is maintained by BMP signals to induce somitic chondrogenesis. Genes Dev 16:1990-2005 |
