| First Author | Sabirzhanova I | Year | 2009 |
| Journal | Dev Growth Differ | Volume | 51 |
| Issue | 4 | Pages | 403-10 |
| PubMed ID | 19366374 | Mgi Jnum | J:148787 |
| Mgi Id | MGI:3846488 | Doi | 10.1111/j.1440-169X.2009.01097.x |
| Citation | Sabirzhanova I, et al. (2009) Activation of Tolloid-like 1 gene expression by the cardiac specific homeobox gene Nkx2-5. Dev Growth Differ 51(4):403-10 |
| abstractText | Mammalian Tolloid-like 1 (Tll-1) is a pleiotropic metalloprotease that is expressed by a small subset of cells within the precardiac mesoderm and is necessary for proper heart development. Following heart tube formation Tll-1 is expressed by the endocardium and regions of myocardium overlying the region of the muscular interventricular septum. Mutations in Tll-1 lead to embryonic lethality due to cardiac defects. We demonstrate that the Tll-1promoter contains Nkx2-5 binding sites and that the Tll-1 promoter is activated by and directly binds Nkx2-5.Tll-1 expression is ablated by a dominant negative Nkx2-5 or by mutation of the Nkx2-5 binding sites within theTll-1 promoter. In vivo, Tll-1 expression is decreased in the hearts of Nkx2-5 knockout embryos when compared with hemizygous and wild-type embryos. These results show that Nkx2-5 is a direct activator of Tll-1 expression and provide insight into the mechanism of the defects found in both the Tll-1 and Nkx2-5 knockout mice. |
