Notch signaling is required for arterial-venous differentiation during embryonic vascular development.
Recent evidence indicates that acquisition of artery or vein identity during vascular development is governed, in part, by genetic mechanisms. The artery-specific expression of a number of Notch signaling genes in mouse and zebrafish suggests that this pathway may play a role in arterial-venous cell fate determination during vascular development. We show that loss of Notch signaling in zebrafish embryos leads to molecular defects in arterial-venous differentiation, including loss of artery-specific markers and ectopic expression of venous markers within the dorsal aorta. Conversely, we find that ectopic activation of Notch signaling leads to repression of venous cell fate. Finally, embryos lacking Notch function exhibit defects in blood vessel formation similar to those associated with improper arterial-venous specification. Our results suggest that Notch signaling is required for the proper development of arterial and venous blood vessels, and that a major role of Notch signaling in blood vessels is to repress venous differentiation within developing arteries. Movies available on-line
Lawson
N D
ND
Laboratory of Molecular Genetics, NICHD, NIH, Bethesda, MD 20892, USA.
Scheer
N
N
Pham
V N
VN
Kim
C H
CH
Chitnis
A B
AB
Campos-Ortega
J A
JA
Weinstein
B M
BM
D000818:Animals; D001158:Arteries / Q000196:embryology*; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology; D004627:Embryonic Induction; D036388:Ephrin-B2; D005260:Female; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008845:Microinjections; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D040321:Vascular Endothelial Growth Factor Receptor-3; D014680:Veins / Q000196:embryology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D036388:Ephrin-B2; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D040321:Vascular Endothelial Growth Factor Receptor-3; D029961:Zebrafish Proteins; C064045:delta protein; C405954:hey2 protein, zebrafish