Whitehead et al. [28] previously reported that loss of Ccm1 leads to vasculature defects in embryo associated with loss of Dll4 and Notch4; and they further demonstrated the down-regulation of Dll4 and Notch4 in vessels of human CCM lesion associated with loss of function mutations in CCM1. The implication of Notch signalling in the angiogenic function of CCM1 was highlighted by a later study by Wüstehube et al. [29]. Here, NOTCH4 is linked to cerebral cavernous malformation.