| First Author | Wu ZQ | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 3998 | PubMed ID | 24894949 |
| Mgi Jnum | J:214991 | Mgi Id | MGI:5604329 |
| Doi | 10.1038/ncomms4998 | Citation | Wu ZQ, et al. (2014) A Snail1/Notch1 signalling axis controls embryonic vascular development. Nat Commun 5:3998 |
| abstractText | Notch1-Delta-like 4 (Dll4) signalling controls vascular development by regulating endothelial cell (EC) targets that modulate vessel wall remodelling and arterial-venous specification. The molecular effectors that modulate Notch signalling during vascular development remain largely undefined. Here we demonstrate that the transcriptional repressor, Snail1, acts as a VEGF-induced regulator of Notch1 signalling and Dll4 expression. EC-specific Snail1 loss-of-function conditional knockout mice die in utero with defects in vessel wall remodelling in association with losses in mural cell investment and disruptions in arterial-venous specification. Snail1 loss-of-function conditional knockout embryos further display upregulated Notch1 signalling and Dll4 expression that is partially reversed by inhibiting gamma-secretase activity in vivo with Dll4 identified as a direct target of Snail1-mediated transcriptional repression. These results document a Snail1-Dll4/Notch1 axis that controls embryonic vascular development. |
