| First Author | Moya IM | Year | 2012 |
| Journal | Dev Cell | Volume | 22 |
| Issue | 3 | Pages | 501-14 |
| PubMed ID | 22364862 | Mgi Jnum | J:182740 |
| Mgi Id | MGI:5316530 | Doi | 10.1016/j.devcel.2012.01.007 |
| Citation | Moya IM, et al. (2012) Stalk cell phenotype depends on integration of Notch and Smad1/5 signaling cascades. Dev Cell 22(3):501-14 |
| abstractText | Gradients of vascular endothelial growth factor (VEGF) induce single endothelial cells to become leading tip cells of emerging angiogenic sprouts. Tip cells then suppress tip-cell features in adjacent stalk cells via Dll4/Notch-mediated lateral inhibition. We report here that Smad1/Smad5-mediated BMP signaling synergizes with Notch signaling during selection of tip and stalk cells. Endothelium-specific inactivation of Smad1/Smad5 in mouse embryos results in impaired Dll4/Notch signaling and increased numbers of tip-cell-like cells at the expense of stalk cells. Smad1/5 downregulation in cultured endothelial cells reduced the expression of several target genes of Notch and of other stalk-cell-enriched transcripts (Hes1, Hey1, Jagged1, VEGFR1, and Id1-3). Moreover, Id proteins act as competence factors for stalk cells and form complexes with Hes1, which augment Hes1 levels in the endothelium. Our findings provide in vivo evidence for a regulatory loop between BMP/TGFbeta-Smad1/5 and Notch signaling that orchestrates tip- versus stalk-cell selection and vessel plasticity. |
