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. 2016 Nov 29;7:13650. doi: 10.1038/ncomms13650

Figure 8. Model for BMP9/10 signalling in maintenance of vascular quiescence.

Figure 8

(a) BMP9/10 signalling through the Alk1 receptor in endothelial cells synergizes with Notch to induce expression of the anti-angiogenic receptor –Vegfr1 thereby repressing Vegf signalling and angiogenesis. Alk1 signalling also represses PI3K activation downstream of Vegfr2 and other growth factors, through inhibition of Pten expression and phosphorylation. PI3K promotes angiogenesis via Akt and downstream activation of ribosomal S6 (pS6), inhibition of Foxo1 and regulation of other downstream effectors. (b) Blocking BMP9/10-Alk1 signalling results in increased Pten expression and phosphorylation, and consequently in an excessive PI3K signalling, thereby inducing vascular defects. Blocking PI3K with PI3K inhibitors rescues excessive angiogenesis and vascular malformations in BMP signalling deficient mice.