Reversal of cerebrovascular anomalies in a zebrafish model of vein of Galen aneurysm
(2025) Nature Cardiovascular Research — (2025)
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- Authors
Martin-Valiente, Edwige 
Vanhollebeke, Benoît Baeyens, Nicolas
- 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.
- Affiliations
Laboratoire de Physiologie et Pharmacologie, Faculté de Médecine Université libre de Bruxelles Laboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles DIAPath, Center for Microscopy and Molecular Imaging (CMMI) Université libre de Bruxelles Transfer, Interfaces and Processes (TIPs), Brussels Engineering School, Université libre de Bruxelles, WEL research institute Department of Interventional Neuroradiology, Erasme Hospital HUB
Citations
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. Published. https://doi.org/10.1038/s44161-025-00659-5 (Original work published 2025)