VEGF-A promotes intussusceptive angiogenesis in the developing chicken chorioallantoic membrane.
OBJECTIVE
To assess the impact of vascular endothelial growth factor (VEGF) on intussusceptive angiogenesis.


RESULTS
Polyurethane casts of the microvasculature of chicken chorioallantoic membrane (CAM) were prepared on embryonic days (E) 8, 10, 12, and 14. At light microscopy level, minute holes (<2 microm in diameter) and hollows (>2 microm) were observed in the casts. Transmission electron microscopy disclosed the minute holes to mainly represent transluminal pillars characteristic for intussusceptive angiogenesis. The numerical density of the holes/pillars was highest at an early (E8) and a late (E12-E14) stage. Only mRNA of VEGF-A-122 and VEGF-A-166 isoforms was detected in the CAM. The transcription rate of VEGF-A mRNA peaked on E8/9 and E12, while VEGF-A protein expression increased on E8/9 and E11/12 to rapidly decrease thereafter as determined by immunoblotting. At all time points investigated, VEGF-A immunohistochemical reactivity was restricted to cells of the chorionic epithelium in direct contact to the capillary plexus. When the VEGF-R-inhibitor PTK787/ZK222584 (0.1 mg/mL) was applied on E9 CAM, the microvasculature topology on E12 was similar to that on E10.


CONCLUSIONS
The temporal course of intussusception corresponded to the expression of VEGF-A in CAM microvasculature. Inhibition of VEGF-signaling retarded intussusceptive-dependent capillary maturation. These data suggest that VEGF promotes intussusception.
Baum
Oliver
O
Institute of Anatomy, University of Bern, Bern 12, Switzerland.
Suter
Florian
F
Gerber
Bernhard
B
Tschanz
Stefan A
SA
Buergy
Regula
R
Blank
Fabian
F
Hlushchuk
Ruslan
R
Djonov
Valentin
V
D000482:Allantois / Q000098:blood supply* / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply* / Q000196:embryology* / Q000378:metabolism; D016319:Corrosion Casting; D008833:Microcirculation; D018919:Neovascularization, Physiologic / Q000235:genetics; D010793:Phthalazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*
D010793:Phthalazines; D011725:Pyridines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C404768:vatalanib