Dosage-sensitive requirement for mouse Dll4 in artery development.
Involvement of the Notch signaling pathway in vascular development has been demonstrated by both gain- and loss-of-function mutations in humans, mice, and zebrafish. In zebrafish, Notch signaling is required for arterial identity by suppressing the venous fate in developing artery cells. In mice, the Notch4 receptor and the Delta-like 4 (Dll4) ligand are specifically expressed in arterial endothelial cells, suggesting a similar role. Here we show that the Dll4 ligand alone is required in a dosage-sensitive manner for normal arterial patterning in development. This implicates Dll4 as the specific mammalian endothelial ligand for autocrine endothelial Notch signaling, and suggests that Dll4 may be a suitable target for intervention in arterial angiogenesis.
Duarte
António
A
CIISA, Faculdade de Medicina Veterinária, 1300-0-477 Lisboa, Portugal.
Hirashima
Masanori
M
Benedito
Rui
R
Trindade
Alexandre
A
Diniz
Patrícia
P
Bekman
Evguenia
E
Costa
Luís
L
Henrique
Domingos
D
Rossant
Janet
J
D000818:Animals; D001158:Arteries / Q000196:embryology* / Q000378:metabolism; D017931:DNA Primers; D042783:Endothelial Cells / Q000378:metabolism; D018628:Gene Dosage; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice / Q000196:embryology*; D008817:Mice, Mutant Strains; D051880:Receptors, Notch; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D051880:Receptors, Notch; C064045:delta protein