TY - JOUR
T1 - Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function
AU - Serini, Guido
AU - Valdembri, Donatella
AU - Zanivan, Sara
AU - Morterra, Giulla
AU - Burkhardt, Constanze
AU - Caccavari, Francesca
AU - Zammataro, Luca
AU - Primo, Luca
AU - Tamagnone, Luca
AU - Logan, Malcolm
AU - Tessier-Lavigne, Marc
AU - Taniguchi, Masahiko
AU - Püschel, Andreas W.
AU - Bussolino, Federico
PY - 2003
Y1 - 2003
N2 - The motility and morphogenesis of endothelial cells is controlled by spatio-temporally regulated activation of integrin adhesion receptors, and integrin activation is stimulated by major determinants of vascular remodelling. In order for endothelial cells to be responsive to changes in activator gradients, the adhesiveness of these cells to the extracellular matrix must be dynamic, and negative regulators of integrins could be required. Here we show that during vascular development and experimental angiogenesis, endothelial cells generate autocrine chemorepulsive signals of class 3 semaphorins (SEMA3 proteins) that localize at nascent adhesive sites in spreading endothelial cells. Disrupting endogenous SEMA3 function in endothelial cells stimulates integrin-mediated adhesion and migration to extracellular matrices, whereas exogenous SEMA3 proteins antagonize integrin activation. Misexpression of dominant negative SEMA3 receptors in chick embryo endothelial cells locks integrins in an active conformation, and severely impairs vascular remodelling. Sema3a null mice show vascular defects as well. Thus during angiogenesis endothelial SEMA3 proteins endow the vascular system with the plasticity required for its reshaping by controlling integrin function.
AB - The motility and morphogenesis of endothelial cells is controlled by spatio-temporally regulated activation of integrin adhesion receptors, and integrin activation is stimulated by major determinants of vascular remodelling. In order for endothelial cells to be responsive to changes in activator gradients, the adhesiveness of these cells to the extracellular matrix must be dynamic, and negative regulators of integrins could be required. Here we show that during vascular development and experimental angiogenesis, endothelial cells generate autocrine chemorepulsive signals of class 3 semaphorins (SEMA3 proteins) that localize at nascent adhesive sites in spreading endothelial cells. Disrupting endogenous SEMA3 function in endothelial cells stimulates integrin-mediated adhesion and migration to extracellular matrices, whereas exogenous SEMA3 proteins antagonize integrin activation. Misexpression of dominant negative SEMA3 receptors in chick embryo endothelial cells locks integrins in an active conformation, and severely impairs vascular remodelling. Sema3a null mice show vascular defects as well. Thus during angiogenesis endothelial SEMA3 proteins endow the vascular system with the plasticity required for its reshaping by controlling integrin function.
KW - Medicine (all)
KW - Multidisciplinary
KW - Medicine (all)
KW - Multidisciplinary
UR - https://publicatt.unicatt.it/handle/10807/141407
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=0041530325&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=0041530325&origin=inward
U2 - 10.1038/nature01784
DO - 10.1038/nature01784
M3 - Article
SN - 0028-0836
VL - 424
SP - 391
EP - 397
JO - Nature
JF - Nature
IS - 6947
ER -