Targeted null-mutation in the vascular endothelial-cadherin gene impairs the organization of vascular-like structures in embryoid bodies.
Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed in endothelial cells and is strictly located at cell-to-cell junctions. As the other members of the cadherin family, VE-cadherin is able to mediate a homotypic type of cellular interaction in a Ca2+-dependent manner. In the mouse embryo, VE-cadherin transcripts are detected at the earliest stages of vascular development. To ascertain if VE-cadherin expression is required for the assembly of endothelial cells into vascular structures, we generated VE-cadherin-negative mouse embryonic stem cells (VE-cadherin-/- ES cells) by gene targeting and examined the consequences on vascular development of ES-derived embryoid bodies (EBs). In contrast to wild-type EBs, we observed that endothelial cells remained dispersed and failed to organize a vessel-like pattern in VE-cadherin-/- ES-derived EBs. However, dispersed VE-cadherin-/- ES-derived endothelial cells expressed a large range of other endothelial markers. Moreover, the targeted null-mutation in the VE-cadherin locus did not interfere with the hematopoietic differentiation potential of ES cells. These in vitro experiments are consistent with a pivotal role of VE-cadherin in vascular structure assembly.
Vittet
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D
Commissariat à l'Energie Atomique, Laboratoire d'Hématologie, Institut National de la Santé et de la Recherche Médicale U217, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France.
Buchou
T
T
Schweitzer
A
A
Dejana
E
E
Huber
P
P
D000818:Animals; D015703:Antigens, CD; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology*; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation; D018274:Electroporation; D005314:Embryonic and Fetal Development; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology*; D019084:Fluorescent Antibody Technique, Indirect; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014162:Transfection; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D000099152:Cadherin 5