PUBLICATION
Apelin signaling drives vascular endothelial cells towards a pro-angiogenic state
- Authors
- Helker, C.S., Eberlein, J., Wilhelm, K., Sugino, T., Malchow, J., Schuermann, A., Baumeister, S., Kwon, H.B., Maischein, H.M., Potente, M., Herzog, W., Stainier, D.Y.
- ID
- ZDB-PUB-201002-107
- Date
- 2020
- Source
- eLIFE 9: e55589 (Journal)
- Registered Authors
- Helker, Christian, Herzog, Wiebke, Maischein, Hans-Martin, Stainier, Didier
- Keywords
- developmental biology, zebrafish
- MeSH Terms
-
- Animals
- Blood Vessels/growth & development*
- Blood Vessels/metabolism
- Chemokines/genetics*
- Chemokines/metabolism
- Endothelial Cells/metabolism
- Morphogenesis/genetics*
- Signal Transduction/genetics*
- Zebrafish/genetics*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 32955436 Full text @ Elife
Citation
Helker, C.S., Eberlein, J., Wilhelm, K., Sugino, T., Malchow, J., Schuermann, A., Baumeister, S., Kwon, H.B., Maischein, H.M., Potente, M., Herzog, W., Stainier, D.Y. (2020) Apelin signaling drives vascular endothelial cells towards a pro-angiogenic state. eLIFE. 9:e55589.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping