PUBLICATION
MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis
- Authors
- Nicoli, S., Standley, C., Walker, P., Hurlstone, A., Fogarty, K.E., and Lawson, N.D.
- ID
- ZDB-PUB-100408-26
- Date
- 2010
- Source
- Nature 464(7292): 1196-1200 (Journal)
- Registered Authors
- Lawson, Nathan, Nicoli, Stefania
- Keywords
- none
- MeSH Terms
-
- Zebrafish/blood
- Zebrafish/embryology
- Zebrafish/genetics*
- Mice
- Vascular Endothelial Growth Factor A/metabolism*
- Kruppel-Like Transcription Factors/metabolism
- Animals
- NIH 3T3 Cells
- Hemodynamics*
- Neovascularization, Physiologic*
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- Gene Expression Regulation, Developmental
- Aorta, Thoracic/embryology*
- Regional Blood Flow/physiology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Intracellular Signaling Peptides and Proteins/genetics
- Intracellular Signaling Peptides and Proteins/metabolism
- Endothelial Cells/metabolism
- Signal Transduction*
- PubMed
- 20364122 Full text @ Nature
Citation
Nicoli, S., Standley, C., Walker, P., Hurlstone, A., Fogarty, K.E., and Lawson, N.D. (2010) MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature. 464(7292):1196-1200.
Abstract
Within the circulatory system, blood flow regulates vascular remodelling, stimulates blood stem cell formation, and has a role in the pathology of vascular disease. During vertebrate embryogenesis, vascular patterning is initially guided by conserved genetic pathways that act before circulation. Subsequently, endothelial cells must incorporate the mechanosensory stimulus of blood flow with these early signals to shape the embryonic vascular system. However, few details are known about how these signals are integrated during development. To investigate this process, we focused on the aortic arch (AA) blood vessels, which are known to remodel in response to blood flow. By using two-photon imaging of live zebrafish embryos, we observe that flow is essential for angiogenesis during AA development. We further find that angiogenic sprouting of AA vessels requires a flow-induced genetic pathway in which the mechano-sensitive zinc finger transcription factor klf2a induces expression of an endothelial-specific microRNA, mir-126, to activate Vegf signalling. Taken together, our work describes a novel genetic mechanism in which a microRNA facilitates integration of a physiological stimulus with growth factor signalling in endothelial cells to guide angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping