Caspase-8 modulates physiological and pathological angiogenesis during retina development
Nathalie Tisch, Aida Freire-Valls, Rosario Yerbes, Isidora Paredes, Silvia La Porta, Xiaohong Wang, Rosa Martin-Perez, Laura Castro, Wendy Wei-Lynn Wong, Leigh Coultas, Boris Strilic, Hermann-Josef Grone, Thomas Hielscher, Carolin Mogler, Ralf H Adams, Peter Heiduschka, Lena Claesson-Welsh, Massimiliano Mazzone, Abelardo Lopez-Rivas, Thomas Schmidt Show all
Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2019
During developmental angiogenesis, blood vessels grow and remodel to ultimately build a hierarchical vascular network. Whether and how cell death signaling molecules contribute to blood vessel formation are still not well understood. Caspase-8 (Casp-8), a key protease in the extrinsic cell death-signaling pathway, regulates cell death via both apoptosis and necroptosis. Here, we show that expression of Casp-8 in endothelial cells (ECs) is required for proper postnatal retina angiogenesis. EC-specific Casp-8-KO pups (Casp-8ECKO) showed reduced retina angiogenesis, as the loss of Casp-8 reduced EC proliferation, sprouting, and migration independently of its cell death function. Instead, the lo..View full abstract
Awarded by Deutsche Forschungsgemeinschaft (DFG)
Awarded by ERC
Awarded by National Health and Research Council (NHMRC)
We thank Manolis Pasparakis for providing MLKL<SUP>KO</SUP> mice and Stephen Hedrick and the UCSD for providing Casp-8<SUP>fl/fl</SUP> mice. We thank Bruno Kohler and Genentech for providing the RIPK3<SUP>KO</SUP> mice. We thank Katie Bentley for her help with the MATLAB image analysis for VE-cadherin staining in vivo. We thank the Nikon imaging Center of the University of Heidelberg for their support. We thank Heike Adler and Melanie Richter for technical assistance and the Ruiz de Almodovar lab for useful discussions. NT was supported by a Heidelberg Biosciences International Graduate School (HBIGS) PhD fellowship; IP was supported by Becas Chile. XW was supported by an Alexander Von Humboldt postdoctoral fellowship. TS is supported by Deutsche Forschungsgemeinschaft (DFG) SCHM 2560/3-1. CRDA is supported by DFG grant RU 1990/1-1, ERC (ERC-StG-311367), and DFG SFB873, FOR2325. CRDA, RHA and HGA are supported by DFG grants from SFB1366 (project number 394046768-SFB 1366). LC is supported by a National Health and Research Council (NHMRC) project grant (1125536) and the L.E.W. Carty Charitable Fund.