Evidence that embryonic kidney cells expressing flk-1 are intrinsic, vasculogenic angioblasts.
Renal glomerular capillary tufts have been believed to arise from angiogenic ingrowth of extrinsic vessels. We found, however, that when embryonic day 12 (E12) mouse kidneys were maintained in culture for 6 days and then grafted into anterior eye chambers of adult transgenic ROSA26 host mice (which carry the beta-galactosidase transgene), glomerular endothelial cells within the grafts were predominantly of intrinsic, kidney origin. To identify potential endothelial precursors, we immunolabled kidneys with antibodies against the vascular endothelial growth factor receptor, flk-1. Numerous discrete cells expressing flk-1 were scattered throughout the nephrogenic mesenchyme of both E12 and newborn kidneys, and with development these cells became concentrated in microvessels, glomerular vascular clefts, and glomerular tufts. In adults, flk-1 was weakly expressed in glomeruli but absent elsewhere. To examine abilities of flk-1-positive cells to establish glomeruli, E12 kidneys were grafted into kidney cortices of adult and newborn ROSA26 hosts. Grafts into adults resulted in few glomeruli containing host-derived endothelium, whereas a majority of glomeruli grafted into newborns contained host cells. Cells of graft origin were found in vessels forming in renal cortices of newborn hosts, but not in adults. Our findings indicate that embryonic kidney cells expressing flk-1 are angioblasts that create microvessels and glomeruli by vasculogenesis.
Robert
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B
Department of Comparative Medicine, University of Alabama at Birmingham 35294-0019, USA.
St John
P L
PL
Hyink
D P
DP
Abrahamson
D R
DR
D000818:Animals; D000867:Anterior Chamber / Q000601:surgery; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D016332:Fetal Tissue Transplantation; D005455:Fluorescent Antibody Technique; D007668:Kidney / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D007672:Kidney Cortex / Q000601:surgery; D037102:Lectins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D009924:Organ Culture Techniques; D037121:Plant Lectins; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor
C045475:Griffonia simplicifolia lectins; D037102:Lectins; D037121:Plant Lectins; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor