The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models

Alina Klems, Jos Rijssel, Anne S. Ramms, Raphael Wild, Julia Hammer, Melanie Merkel, Laura Derenbach, Laetitia Préau, Rabea Hinkel, Irina Suarez-Martinez, Stefan Schulte-Merker, Ramon Vidal, Sascha Sauer, Riikka Kivelä, Kari Alitalo, Christian Kupatt, Jaap D. Buul and Ferdinand Noble ()
Additional contact information
Alina Klems: Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT)
Jos Rijssel: Sanquin Research and Landsteiner Laboratory, Academic Medical Center at the University of Amsterdam
Anne S. Ramms: Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT)
Raphael Wild: Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT)
Julia Hammer: Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT)
Melanie Merkel: Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT)
Laura Derenbach: Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT)
Laetitia Préau: Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT)
Rabea Hinkel: Germany and DZHK (German Center for Cardiovascular Research)
Irina Suarez-Martinez: Institute of Cardiovascular Organogenesis and Regeneration WWU Münster, Münster, Germany & Faculty of Medicine, WWU Münster, Münster, Germany & Cells in Motion Cluster of Excellence, Münster
Stefan Schulte-Merker: Institute of Cardiovascular Organogenesis and Regeneration WWU Münster, Münster, Germany & Faculty of Medicine, WWU Münster, Münster, Germany & Cells in Motion Cluster of Excellence, Münster
Ramon Vidal: Berlin Institute of Medical Systems Biology & Berlin Institute of Health
Sascha Sauer: Berlin Institute of Medical Systems Biology & Berlin Institute of Health
Riikka Kivelä: University of Helsinki, and Wihuri Research Institute
Kari Alitalo: University of Helsinki, and Wihuri Research Institute
Christian Kupatt: (German Center for Cardiovascular Research)
Jaap D. Buul: Sanquin Research and Landsteiner Laboratory, Academic Medical Center at the University of Amsterdam
Ferdinand Noble: Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT)

Nature Communications, 2020, vol. 11, issue 1, 1-20

Abstract: Abstract Arterial networks enlarge in response to increase in tissue metabolism to facilitate flow and nutrient delivery. Typically, the transition of a growing artery with a small diameter into a large caliber artery with a sizeable diameter occurs upon the blood flow driven change in number and shape of endothelial cells lining the arterial lumen. Here, using zebrafish embryos and endothelial cell models, we describe an alternative, flow independent model, involving enlargement of arterial endothelial cells, which results in the formation of large diameter arteries. Endothelial enlargement requires the GEF1 domain of the guanine nucleotide exchange factor Trio and activation of Rho-GTPases Rac1 and RhoG in the cell periphery, inducing F-actin cytoskeleton remodeling, myosin based tension at junction regions and focal adhesions. Activation of Trio in developing arteries in vivo involves precise titration of the Vegf signaling strength in the arterial wall, which is controlled by the soluble Vegf receptor Flt1.

Date: 2020
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DOI: 10.1038/s41467-020-19008-0

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