| First Author | Zhao M | Year | 2013 |
| Journal | Mol Cell Biol | Volume | 33 |
| Issue | 16 | Pages | 3099-112 |
| PubMed ID | 23754753 | Mgi Jnum | J:204561 |
| Mgi Id | MGI:5532804 | Doi | 10.1128/MCB.00524-13 |
| Citation | Zhao M, et al. (2013) A network of transcription factors operates during early tooth morphogenesis. Mol Cell Biol 33(16):3099-112 |
| abstractText | Improving the knowledge of disease-causing genes is a unique challenge in human health. Although it is known that genes causing similar diseases tend to lie close to one another in a network of protein-protein or functional interactions, the identification of these protein-protein networks is difficult to unravel. Here, we show that Msx1, Snail, Lhx6, Lhx8, Sp3, and Lef1 interact in vitro and in vivo, revealing the existence of a novel context-specific protein network. These proteins are all expressed in the neural crest-derived dental mesenchyme and cause tooth agenesis disorder when mutated in mouse and/or human. We also identified an in vivo direct target for Msx1 function, the cyclin D-dependent kinase (CDK) inhibitor p19(ink4d), whose transcription is differentially modulated by the protein network. Considering the important role of p19(ink4d) as a cell cycle regulator, these results provide evidence for the first time of the unique plasticity of the Msx1-dependent network of proteins in conferring differential transcriptional output and in controlling the cell cycle through the regulation of a cyclin D-dependent kinase inhibitor. Collectively, these data reveal a novel protein network operating in the neural crest-derived dental mesenchyme that is relevant for many other areas of developmental and evolutionary biology. |
