Apelin signaling drives vascular endothelial cells towards a pro-angiogenic state
- Philipps-University Marburg, Germany
- Max Planck Institute for Heart and Lung Research, Germany
- University of Muenster, Germany
Abstract
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, and its function is required for the hypersprouting phenotype in Delta-like 4 (Dll4) knockdown 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Christian SM Helker
Didier YR Stainier
Funding
Deutsche Forschungsgemeinschaft (SFB 834)
- Didier YR Stainier
North Rhine-Westphalia (return fellowship')
- Wiebke Herzog
Deutsche Forschungsgemeinschaft (SFB 834)
- Christian SM Helker
Deutsche Forschungsgemeinschaft (GRK2213)
- Christian SM Helker
Deutsche Forschungsgemeinschaft (GRK2213)
- Jean Eberlein
Deutsche Forschungsgemeinschaft (GRK2213)
- Julian Malchow
Deutsche Forschungsgemeinschaft (HE4585/3-1)
- Wiebke Herzog
H2020 European Research Council (EMERGE (773047))
- Michael Potente
Deutsche Forschungsgemeinschaft (EXC 2026)
- Michael Potente
H2020 European Research Council (AdG project: ZMOD 694455)
- Didier YR Stainier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Ethics StatementAll zebrafish husbandry was performed under standard conditions, and all experiments were conducted in accordance with institutional (MPG) and national ethical and animal welfare guidelines (Proposal numbers: B2/1017, B2/1041, B2/1218, B2/1138). All procedures conform to the guidelines from Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes.
Copyright
© 2020, Helker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Apelin signaling drives vascular endothelial cells towards a pro-angiogenic state
eLife 9:e55589.
https://doi.org/10.7554/eLife.55589
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