Hedgehog signaling is essential for endothelial tube formation during vasculogenesis.
During embryonic development, the first blood vessels are formed through the aggregation and subsequent assembly of angioblasts (endothelial precursors) into a network of endothelial tubes, a process known as vasculogenesis. These first vessels generally form in mesoderm that is adjacent to endodermal tissue. Although specification of the angioblast lineage is independent of endoderm interactions, a signal from the endoderm is necessary for angioblasts to assemble into a vascular network and to undergo vascular tube formation. In this study, we show that endodermally derived sonic hedgehog is both necessary and sufficient for vascular tube formation in avian embryos. We also show that Hedgehog signaling is required for vascular tube formation in mouse embryos, and for vascular cord formation in cultured mouse endothelial cells. These results demonstrate a previously uncharacterized role for Hedgehog signaling in vascular development, and identify Hedgehog signaling as an important component of the molecular pathway leading to vascular tube formation.
Department of Cell Biology and Anatomy, University of Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, AZ 85724-5044, USA.
Steven A
SA
Vokes
Tatiana A
TA
Yatskievych
Ronald L
RL
Heimark
Jill
J
McMahon
Andrew P
AP
McMahon
Parker B
PB
Antin
Paul A
PA
Krieg
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004707:Endoderm / Q000378:metabolism; D004727:Endothelium / Q000166:cytology* / Q000196:embryology*; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D009389:Neovascularization, Pathologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017931:DNA Primers; D053823:Hedgehog Proteins; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A