Extended Data Figure 4. Map3k3 haploinsufficiency rescues both early embryonic lethality due to endothelial loss of Krit1 and postnatal CCM lesion formation due to endothelial loss of Ccm2.

a, Partial loss of MEKK3 rescues early lethality associated with endothelial deletion of Krit1. E10.5 littermate embryos are shown. Tie2-Cre;Krit1^fl/fl animals lacking endothelial KRIT1 die by E9.5 due to lack of patent branchial arch arteries (middle). In contrast, Tie2-Cre;Krit1^fl/fl;Map3k3^fl/+ animals develop patent arteries and survive past mid-gestation (right). Note the presence of pericardial edema due to a persistent cardiac defect in the Tie2-Cre;Krit1^fl/fl;Map3k3^fl/+ embryo. Images are representative of 3 independent experiments. b, Rescue of CCM formation in the Ccm2 model with loss of MEKK3. VE-cadherin CreERT2;Ccm2^fl/fl; Map3k3^+/+ (“Ccm2^ECKO”) and VE-cadherin CreERT2;Ccm2^fl/fl; Map3k3^fl/+ neonates were induced with tamoxifen at P1 and lesion formation scored by visual detection in the hindbrain at P11 as done for Krit1^ECKO animals. Images are representative of 4 independent experiments.