PUBLICATION
Live-imaging of endothelial Erk activity reveals dynamic and sequential signalling events during regenerative angiogenesis
- Authors
- Okuda, K.S., Keyser, M.S., Gurevich, D.B., Sturtzel, C., Mason, E.A., Paterson, S., Chen, H., Scott, M., Condon, N.D., Martin, P., Distel, M., Hogan, B.M.
- ID
- ZDB-PUB-210519-28
- Date
- 2021
- Source
- eLIFE 10: (Journal)
- Registered Authors
- Distel, Martin, Hogan, Ben M., Martin, Paul, Mason, Elizabeth, Okuda, Kazuhide Shaun, Paterson, Scott, Sturtzel, Caterina
- Keywords
- developmental biology, zebrafish
- MeSH Terms
-
- Animals
- Cells, Cultured
- Endothelial Cells/metabolism*
- Image Processing, Computer-Assisted/methods*
- MAP Kinase Signaling System/genetics
- MAP Kinase Signaling System/physiology*
- Neovascularization, Pathologic/metabolism*
- Neovascularization, Physiologic*
- Signal Transduction*
- Vascular Endothelial Growth Factor A/metabolism
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- Zebrafish
- PubMed
- 34003110 Full text @ Elife
Citation
Okuda, K.S., Keyser, M.S., Gurevich, D.B., Sturtzel, C., Mason, E.A., Paterson, S., Chen, H., Scott, M., Condon, N.D., Martin, P., Distel, M., Hogan, B.M. (2021) Live-imaging of endothelial Erk activity reveals dynamic and sequential signalling events during regenerative angiogenesis. eLIFE. 10:.
Abstract
The formation of new blood vessel networks occurs via angiogenesis during development, tissue repair and disease. Angiogenesis is regulated by intracellular endothelial signalling pathways, induced downstream of Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). A major challenge in understanding angiogenesis is interpreting how signalling events occur dynamically within endothelial cell populations during sprouting, proliferation and migration. Erk is a central downstream effector of Vegf-signalling and reports the signalling that drives angiogenesis. We generated a vascular Erk biosensor transgenic line in zebrafish using a kinase translocation reporter that allows live-imaging of Erk-signalling dynamics. We demonstrate the utility of this line to live-image Erk activity during physiologically relevant angiogenic events. Further, we reveal dynamic and sequential endothelial cell Erk-signalling events following blood vessel wounding. Initial signalling is dependent upon Ca2+ in the earliest responding endothelial cells, but is independent of Vegfr-signalling and local inflammation. The sustained regenerative response however, involves a Vegfr-dependent mechanism that initiates concomitant with the wound inflammatory response. This work reveals a highly dynamic sequence of signalling events in regenerative angiogenesis and validates a new resource for the study of vascular Erk-signalling in real-time.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping