Negative regulation of midline vascular development by the notochord.
The negative regulation of vascular patterning is one of the least understood processes in vascular biology. In amniotes, blood vessels develop throughout the embryonic disc, except for a midline region surrounding the notochord. Here we show that the notochord is the primary signaling center for the inhibition of vessel formation along the embryonic midline. Notochord ablation in quail embryos results in vascular plexus formation at midline. Implantation of the notochord into paraxial and lateral mesoderm inhibits vessel formation locally. The notochord-expressed BMP antagonists Chordin and Noggin inhibit endothelial cell migration in vitro, and their ectopic expression in vivo results in a local disruption of vessel formation. Conversely, BMP-4 activates endothelial cell migration in vitro, and its ectopic expression along the notochord induces vascular plexus formation at midline. These data indicate an inhibitory role of the notochord in defining an avascular zone at the embryonic midline, in part via BMP antagonism.
Reese
David E
DE
Department of Cell and Developmental Biology, Cornell University Medical College, 1300 York Avenue, New York, NY 10021, USA.
Hall
Christopher E
CE
Mikawa
Takashi
T
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D019521:Body Patterning / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002352:Carrier Proteins; D002465:Cell Movement / Q000502:physiology; D002828:Choristoma / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000196:embryology*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D009672:Notochord / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D019899:Paracrine Communication / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D011784:Quail / Q000196:embryology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099176:Noggin Protein
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A; D000099176:Noggin Protein; C054234:chordin