A Snail1/Notch1 signalling axis controls embryonic vascular development

作者：Wu Zhao Qiu; Rowe R Grant; Lim Kim Chew; Lin Yongshun; Willis Amanda; Tang Yi; Li Xiao Yan; Nor Jacques E; Maillard Ivan; Weiss Stephen J^*

来源：Nature Communications, 2014, 5(1): 3998.

DOI：10.1038/ncomms4998

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.

• 出版日期2014-6