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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR048487-02
Application #
6622346
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Tyree, Bernadette
Project Start
2002-04-01
Project End
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
2
Fiscal Year
2003
Total Cost
$49,862
Indirect Cost
Name
Harvard University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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