Liver organogenesis promoted by endothelial cells prior to vascular function.
The embryonic role of endothelial cells and nascent vessels in promoting organogenesis, prior to vascular function, is unclear. We find that early endothelial cells in mouse embryos surround newly specified hepatic endoderm and delimit the mesenchymal domain into which the liver bud grows. In flk-1 mutant embryos, which lack endothelial cells, hepatic specification occurs, but liver morphogenesis fails prior to mesenchyme invasion. We developed an embryo tissue explant system that permits liver bud vasculogenesis and show that in the absence of endothelial cells, or when the latter are inhibited, there is a selective defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.
Matsumoto
K
K
Cell and Developmental Biology Program, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
Yoshitomi
H
H
Rossant
J
J
Zaret
K S
KS
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology / Q000502:physiology; D046508:Culture Techniques; D004627:Embryonic Induction; D004707:Endoderm / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D022781:Hepatocytes / Q000502:physiology; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D008297:Male; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008934:Mitogens; D009024:Morphogenesis; D009154:Mutation; D018919:Neovascularization, Physiologic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D017978:Receptors, Growth Factor / Q000235:genetics / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor; D015398:Signal Transduction / Q000187:drug effects
C066855:HGF protein, human; D008934:Mitogens; D017978:Receptors, Growth Factor; D017228:Hepatocyte Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor