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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.

The mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand exhibit happloinsufficient lethality because of defects in vascular remodeling is reported. Notch pathway mutant embryos exhibit defects in arterial specification of nascent blood vessels and develop arteriovenous malformations.

Research has been conducted on the role of the Notch4 gene in the intercellular signaling mechanism. The generation of the Notch4-deficient mice by gene targeting is described.

Research has been conducted on D114 gene of the Notch ligands. The results of the cloning and characterization of this gene are presented.

Growth retardation and postnatal mortality accompanies embryogenesis in bcl-2-l-mice characterized by the absence of the oncogene, bcl-2. Polycystic kidney disease, fulminant apoptosis of the thymus and spleen and cell death in thymocytes commonly prevail in the bcl-2-l-mice. Programmed cell death is ascribed to the function of oxygen-induced free radicals. Bcl-2 is characterized by a death repressor molecular activity which proceeds through an antioxidant pathway.

Studies of Hox11-/- genes lacking spleen reveal that, despite the absence of cellular organization at the site of splenic development, other splanchnic derivatives develop normally. Hox11 gene appear to control the organogenesis of spleen. The Hox11 ablation results in asplenia.