DLL4 and cerebral cavernous malformation: On the other hand, it has been reported that KRIT1 inactivation in ECs leads to the downregulation of Notch target genes, including HEY1 and HEY2, and of the Notch ligand Delta-like 4 (Dll4), which contribute to abnormal angiogenic responses and impaired EC-pericyte interactions associated with the pathogenesis of CCM disease [14,15,68].