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About the Authors:
Patricia Molina-Ortiz
Contributed equally to this work with: Patricia Molina-Ortiz, Tanguy Orban
Roles Conceptualization, Formal analysis, Investigation, Methodology, Writing - review & editing
Affiliation: Laboratory of Functional Genetics, GIGA-Molecular Biology of Disease, University of Liège, Liège, Belgium
ORCID http://orcid.org/0000-0003-2654-2433
Tanguy Orban
Contributed equally to this work with: Patricia Molina-Ortiz, Tanguy Orban
Roles Conceptualization, Formal analysis, Investigation, Methodology, Writing - review & editing
Affiliation: Laboratory of Protein signaling and Interactions Signalisation, GIGA-Molecular Biology of Diseases, University of Liège, Liège, Belgium
Maud Martin
Roles Formal analysis, Investigation, Methodology, Writing - review & editing
Current address: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, the Netherlands
Affiliations Laboratory of Functional Genetics, GIGA-Molecular Biology of Disease, University of Liège, Liège, Belgium, Laboratory of Protein signaling and Interactions Signalisation, GIGA-Molecular Biology of Diseases, University of Liège, Liège, Belgium
Audrey Habets
Roles Formal analysis, Investigation, Methodology
Affiliation: Laboratory of Protein signaling and Interactions Signalisation, GIGA-Molecular Biology of Diseases, University of Liège, Liège, Belgium
Franck Dequiedt
Roles Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing
¶‡ FD and SS also contributed equally to this work.
Affiliation: Laboratory of Protein signaling and Interactions Signalisation, GIGA-Molecular Biology of Diseases, University of Liège, Liège, Belgium
ORCID http://orcid.org/0000-0003-1234-7477
Stéphane Schurmans
Roles Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing
* E-mail: [email protected]
¶‡ FD and SS also contributed equally to this work.
Affiliation: Laboratory of Functional Genetics, GIGA-Molecular Biology of Disease, University of Liège, Liège, Belgium
ORCID http://orcid.org/0000-0002-5579-3840Abstract
Rasa3 is a GTPase activating protein of the GAP1 family which targets R-Ras and Rap1. Although catalytic inactivation or deletion of Rasa3 in mice leads to severe hemorrhages and embryonic lethality, the biological function and cellular location of Rasa3 underlying these defects remains unknown. Here, using a combination of loss of function studies in mouse and zebrafish as well as in vitro cell biology approaches, we identify a key role for Rasa3 in endothelial cells and vascular lumen integrity. Specific ablation of Rasa3 in the mouse endothelium, but not in megakaryocytes and platelets, lead to embryonic bleeding and death at mid-gestation, recapitulating the phenotype observed in full Rasa3 knock-out mice. Reduced plexus/sprouts formation and...