Fig. 8. Schematic representation of TGFβ signalling in ECs and VSMCs in TGFβ-receptor mutant embryos. See key (bottom) for details. (A) In wild-type embryos, SMAD2 is phosphorylated by ALK5 in both ECs and VSMCs, whereas SMAD1 is phosphorylated by ALK1 in ECs. (B) When ALK5 is deleted specifically in ECs, PSMAD2 is no longer detected in either cell type. Additionally, PSMAD1 is also lost, because ALK1 activity requires ALK5. (C) In ALK5^–/– yolk sacs, ALK4 is upregulated in both ECs and VSMCs; this rescues SMAD2 phosphorylation, but ALK1 is still not able to phosphorylate SMAD1. (D) However, in the presence of the ALK5 mutant (D266A), ALK1 is able to phosphorylate SMAD1 in ECs. In VSMCs, SMAD2 is again phosphorylated via the upregulation of ALK4.