| First Author | Nobuhisa I | Year | 2004 |
| Journal | J Exp Med | Volume | 199 |
| Issue | 5 | Pages | 737-42 |
| PubMed ID | 14981116 | Mgi Jnum | J:90463 |
| Mgi Id | MGI:3043902 | Doi | 10.1084/jem.20030830 |
| Citation | Nobuhisa I, et al. (2004) Spred-2 Suppresses Aorta-Gonad-Mesonephros Hematopoiesis by Inhibiting MAP Kinase Activation. J Exp Med 199(5):737-42 |
| abstractText | In midgestation mouse embryos, the aorta-gonad-mesonephros (AGM) region generates hematopoietic stem cells and definitive hematopoiesis is regulated by cell-cell interaction and signaling molecules. We showed that a Ras/mitogen-activated protein (MAP) kinase signaling-specific inhibitor and a dominant negative mutant Ras blocked the production of CD45(+) hematopoietic cells in embryonic day 11.5 AGM culture, indicating an essential role for the MAP kinase pathway in AGM hematopoiesis. Overexpression of the Ras/MAP kinase pathway regulator, Spred-2, in the AGM culture significantly reduced the number of CD45(+) cells. In contrast, production of CD45(+) cells from the AGM region of Spred-2-null mice was up-regulated as compared with wild-type littermates. Furthermore, Spred-2-deficient mice exhibited elevated hematopoietic colony formation from vascular endothelial-cadherin(+) cells. These data indicate that Spred-2 functions as a negative regulator of AGM hematopoiesis by inhibiting hematopoietic cytokine signaling. |
