Vegf as an epithelial cell morphogen modulates branching morphogenesis of embryonic kidney by directly acting on the ureteric bud.
There is growing evidence that vascular endothelial growth factor (Vegf), a well-recognized angiogenic factor, plays a regulatory role in non-endothelial tissues such as neurons and epithelial cells. In the kidney Vegf receptors have been detected in proximal tubule cells of the adult kidney and Vegf has been show to stimulate branching morphogenesis of the developing kidney. In this study, using laser-microdissection as well as manual separation of the UB, we demonstrate that Vegf receptors are present in the ureteric bud (UB). Furthermore, we determine that Vegf stimulates UB branching in whole kidney explant that is mediated directly by signaling through Vegfr2. In addition, Vegf also induced branching response in isolated UBs that are free of the surrounding mesenchyme. These responses seem to be strictly dependent on the dose of Vegf such that higher doses are inhibitory while lower dose are stimulatory. These data place Vegf in a unique position of being able to modulate vascular as well as epithelial development in the embryonic kidney.
Marlier
Arnaud
A
Section of Nephrology, Department of Medicine, Yale University School of Medicine, 1 Gillbert St. TAC S-240, New Haven, CT 06510, USA.
Schmidt-Ott
Kai M
KM
Gallagher
Anna-Rachel
AR
Barasch
Jonathan
J
Karihaloo
Anil
A
D000818:Animals; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000196:embryology; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014513:Ureter / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2