Involvement of the Notch pathway in vascular devolvement is demonstrated by both gain -and loss-of-function mutations in humans  mice  and zebrafish The Delta-like 4 (D114) ligand alone is required in a dossage-sensitive manner for normal arterial patterning in development  which implicates D114 as the specific mammalian endothelial for autocrine endothelial Notch signaling