Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function

Guido Serini (), Donatella Valdembri, Sara Zanivan, Giulia Morterra, Constanze Burkhardt, Francesca Caccavari, Luca Zammataro, Luca Primo, Luca Tamagnone, Malcolm Logan, Marc Tessier-Lavigne, Masahiko Taniguchi, Andreas W. Püschel and Federico Bussolino ()
Additional contact information
Guido Serini: University of Torino School of Medicine
Donatella Valdembri: University of Torino School of Medicine
Sara Zanivan: University of Torino School of Medicine
Giulia Morterra: University of Torino School of Medicine
Constanze Burkhardt: Westfälische Wilhelms-Universität
Francesca Caccavari: University of Torino School of Medicine
Luca Zammataro: University of Torino School of Medicine
Luca Primo: University of Torino School of Medicine
Luca Tamagnone: University of Torino School of Medicine
Malcolm Logan: National Institute for Medical Research
Marc Tessier-Lavigne: Stanford University
Masahiko Taniguchi: University of Tokyo
Andreas W. Püschel: Westfälische Wilhelms-Universität
Federico Bussolino: University of Torino School of Medicine

Nature, 2003, vol. 424, issue 6947, 391-397

Abstract: Abstract 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.

Date: 2003
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature01784 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:424:y:2003:i:6947:d:10.1038_nature01784

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01784

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().