De Smet, F., Tembuyser, B., Lenard, A., Claes, F., Zhang, J., Michielsen, C., Van Schepdael, A., Herbert, J.M., Bono, F., Affolter, M., Dewerchin, M., Carmeliet, P. (2014) Fibroblast Growth Factor Signaling Affects Vascular Outgrowth and Is Required for the Maintenance of Blood Vessel Integrity. Chemistry & Biology. 21(10):1310-7.
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.