title: Fibroblast growth factor signaling affects vascular outgrowth and is required for the maintenance of blood vessel integrity.
abstract: Angiogenesis contributes to the development of numerous disorders. Even though fibroblast growth factors (FGFs) were discovered as mediators of angiogenesis more than 30 years ago, their role in developmental angiogenesis still remains elusive. We use a recently described chemical probe, SSR128129E (SSR), that selectively inhibits the action of multiple FGF receptors (FGFRs), in combination with the zebrafish model to examine the role of FGF signaling in vascular development. We observe that while FGFR signaling is less important for vessel guidance, it affects vascular outgrowth and is especially required for the maintenance of blood vessel integrity by ensuring proper cell-cell junctions between endothelial cells. In conclusion, our work illustrates the power of a small molecule probe to reveal insights into blood vessel formation and stabilization and thus of broad interest to the vascular biology community.
authors.affiliation: Laboratory of Angiogenesis & Neurovascular Link, Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis & Neurovascular Link, Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Frederik
authors.initials: F
authors.lastname: De Smet
authors.affiliation: Laboratory of Angiogenesis & Neurovascular Link, Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis & Neurovascular Link, Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Bieke
authors.initials: B
authors.lastname: Tembuyser
authors.affiliation: Biozentrum der Universität Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lenard
authors.affiliation: Laboratory of Angiogenesis & Neurovascular Link, Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis & Neurovascular Link, Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Claes
authors.affiliation: Laboratory of Pharmaceutical Analysis, Pharmaceutical Sciences, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Pharmaceutical Analysis, Pharmaceutical Sciences, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Christof
authors.initials: C
authors.lastname: Michielsen
authors.affiliation: Laboratory of Pharmaceutical Analysis, Pharmaceutical Sciences, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Van Schepdael
authors.affiliation: Early to Candidate Department and Lead Generation and Candidate Realization Department, Sanofi, 31036 Toulouse, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Herbert
authors.affiliation: Early to Candidate Department and Lead Generation and Candidate Realization Department, Sanofi, 31036 Toulouse, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Bono
authors.affiliation: Biozentrum der Universität Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Affolter
authors.affiliation: Laboratory of Angiogenesis & Neurovascular Link, Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis & Neurovascular Link, Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.affiliation: Laboratory of Angiogenesis & Neurovascular Link, Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis & Neurovascular Link, Department of Oncology, KU Leuven, 3000 Leuven, Belgium. Electronic address: peter.carmeliet@vib-kuleuven.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
mesh_terms: D058500:Animal Fins / Q000502:physiology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D007212:Indolizines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007365:Intercellular Junctions / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012038:Regeneration; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015820:Cadherins; D007212:Indolizines; D017468:Receptors, Fibroblast Growth Factor; C000593029:SSR128129E; D029961:Zebrafish Proteins; D062367:ortho-Aminobenzoates