N-cadherin deficiency impairs pericyte recruitment, and not endothelial differentiation or sprouting, in embryonic stem cell-derived angiogenesis.
Endothelial cells express two classical cadherins, VE-cadherin and N-cadherin. VE-cadherin is absolutely required for vascular morphogenesis, but N-cadherin is thought to participate in vessel stabilization by interacting with periendothelial cells during vessel formation. However, recent data suggest a more critical role for N-cadherin in endothelium that would regulate angiogenesis, in part by controlling VE-cadherin expression. In this study, we have assessed N-cadherin function in vascular development using an in vitro model derived from embryonic stem (ES) cell differentiation. We show that pluripotent ES cells genetically null for N-cadherin can differentiate normally into endothelial cells. In addition, sprouting angiogenesis was unaltered, suggesting that N-cadherin is not essential for the early events of angiogenesis. However, the lack of N-cadherin led to an impairment in pericyte covering of endothelial outgrowths. We conclude that N-cadherin is necessary neither for vasculogenesis nor proliferation and migration of endothelial cells but is required for the subsequent maturation of endothelial sprouts by interacting with pericytes.
Tillet
Emmanuelle
E
Laboratoire de Développement et Vieillissement de l'Endothelium, INSERM EMI 0219; CEA; Joseph Fourier University, Grenoble, France. emmanuelle.tillet@cea.fr
Vittet
Daniel
D
Féraud
Olivier
O
Moore
Robert
R
Kemler
Rolf
R
Huber
Philippe
P
D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D004622:Embryo, Mammalian / Q000166:cytology; D042783:Endothelial Cells / Q000737:chemistry / Q000502:physiology; D051379:Mice; D009154:Mutation; D018919:Neovascularization, Physiologic / Q000235:genetics; D020286:Pericytes / Q000737:chemistry / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism
D015820:Cadherins