TY - JOUR TI - Apelin signaling drives vascular endothelial cells toward a pro-angiogenic state AU - Helker, Christian SM AU - Eberlein, Jean AU - Wilhelm, Kerstin AU - Sugino, Toshiya AU - Malchow, Julian AU - Schuermann, Annika AU - Baumeister, Stefan AU - Kwon, Hyouk-Bum AU - Maischein, Hans-Martin AU - Potente, Michael AU - Herzog, Wiebke AU - Stainier, Didier YR A2 - Burns, Caroline E A2 - Bronner, Marianne E A2 - Mochizuki, Naoki VL - 9 PY - 2020 DA - 2020/09/21 SP - e55589 C1 - eLife 2020;9:e55589 DO - 10.7554/eLife.55589 UR - https://doi.org/10.7554/eLife.55589 AB - To form new blood vessels (angiogenesis), endothelial cells (ECs) must be activated and acquire highly migratory and proliferative phenotypes. However, the molecular mechanisms that govern these processes are incompletely understood. Here, we show that Apelin signaling functions to drive ECs into such an angiogenic state. Zebrafish lacking Apelin signaling exhibit defects in endothelial tip cell morphology and sprouting. Using transplantation experiments, we find that in mosaic vessels, wild-type ECs leave the dorsal aorta (DA) and form new vessels while neighboring ECs defective in Apelin signaling remain in the DA. Mechanistically, Apelin signaling enhances glycolytic activity in ECs at least in part by increasing levels of the growth-promoting transcription factor c-Myc. Moreover, APELIN expression is regulated by Notch signaling in human ECs, and its function is required for the hypersprouting phenotype in Delta-like 4 (Dll4) knockdown zebrafish embryos. These data provide new insights into fundamental principles of blood vessel formation and Apelin signaling, enabling a better understanding of vascular growth in health and disease. KW - apelin KW - notch KW - metabolism KW - angiogenesis KW - endothelial cells KW - sprouting JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -