PUBLICATION
Reversal of cerebrovascular anomalies in a zebrafish model of vein of Galen aneurysm
- Authors
- Martin-Valiente, E., Du, Y., Goemans, C., America, M., Zindy, E., Adam, M., Scheid, B., Vikkula, M., Lubicz, B., Vanhollebeke, B., Baeyens, N.
- ID
- ZDB-PUB-250613-1
- Date
- 2025
- Source
- Nature cardiovascular research : (Journal)
- Registered Authors
- Vanhollebeke, Benoit
- Keywords
- none
- MeSH Terms
-
- Disease Models, Animal
- Cerebrovascular Circulation*
- Endothelial Cells/metabolism
- Endothelial Cells/pathology
- Vein of Galen Malformations*/genetics
- Vein of Galen Malformations*/metabolism
- Vein of Galen Malformations*/physiopathology
- p120 GTPase Activating Protein*/deficiency
- p120 GTPase Activating Protein*/genetics
- p120 GTPase Activating Protein*/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Animals
- Cerebral Veins*/abnormalities
- Cerebral Veins*/metabolism
- Cerebral Veins*/physiopathology
- Phenotype
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Receptor, EphB4/deficiency
- Receptor, EphB4/genetics
- Receptor, EphB4/metabolism
- Signal Transduction
- Animals, Genetically Modified
- Phosphatidylinositol 3-Kinases/metabolism
- PubMed
- 40506481 Full text @ Nat Cardiovasc Res
Citation
Martin-Valiente, E., Du, Y., Goemans, C., America, M., Zindy, E., Adam, M., Scheid, B., Vikkula, M., Lubicz, B., Vanhollebeke, B., Baeyens, N. (2025) Reversal of cerebrovascular anomalies in a zebrafish model of vein of Galen aneurysm. Nature cardiovascular research. :.
Abstract
Congenital vascular malformations result from abnormal development of the vascular tree, with the aneurysmal malformation of the vein of Galen (VGAM) being the most prevalent neurovascular malformation in neonates, associated with poor outcomes. This condition is linked to germline mutations in the RASA1 and EPHB4 genes, although the underlying developmental mechanisms remain unclear. Here we generate zebrafish models lacking rasa1a and ephb4a that replicate the genetic and structural features of VGAMs. Our findings connect the development of malformations to insufficient fusion of precursor blood vessels, a process regulated by blood flow and the responses of endothelial cells. RASA1 deficiency destabilizes the homeostatic response to blood flow and contributes to impaired flow-mediated activation of MAPK and phosphatidylinositol-3-kinase signaling. By pharmacologically targeting these signaling pathways in mutant models, we restore normal fusion in existing malformations, offering potential new strategies for treating VGAMs and similar vascular remodeling disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping