Cdh5/VE-cadherin promotes endothelial cell interface elongation via cortical actin polymerization during angiogenic sprouting.
Organ morphogenesis requires the coordination of cell behaviors. Here, we have analyzed dynamic endothelial cell behaviors underlying sprouting angiogenesis in vivo. Two different mechanisms contribute to sprout outgrowth: tip cells show strong migratory behavior, whereas extension of the stalk is dependent upon cell elongation. To investigate the function of Cdh5 in sprout outgrowth, we generated null mutations in the zebrafish cdh5 gene, and we found that junctional remodeling and cell elongation are impaired in mutant embryos. The defects are associated with a disorganization of the actin cytoskeleton and cannot be rescued by expression of a truncated version of Cdh5. Finally, the defects in junctional remodeling can be phenocopied by pharmacological inhibition of actin polymerization, but not by inhibiting actin-myosin contractility. Taken together, our results support a model in which Cdh5 organizes junctional and cortical actin cytoskeletons, as well as provides structural support for polymerizing F-actin cables during endothelial cell elongation.
Biozentrum der Universität Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Loïc
L
Sauteur
Biozentrum der Universität Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Alice
A
Krudewig
Biozentrum der Universität Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Lukas
L
Herwig
Biozentrum der Universität Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Nikolaus
N
Ehrenfeuchter
Biozentrum der Universität Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Anna
A
Lenard
Biozentrum der Universität Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland. Electronic address: markus.affolter@unibas.ch.
Markus
M
Affolter
Biozentrum der Universität Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland. Electronic address: heinz-georg.belting@unibas.ch.
Heinz-Georg
HG
Belting
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D004730:Endothelium, Vascular / Q000196:embryology / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D018919:Neovascularization, Physiologic; D058105:Polymerization; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D000099152:Cadherin 5
D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D009218:Myosins; D000099152:Cadherin 5