TY - JOUR
T1 - The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models
AU - Klems, Alina
AU - van Rijssel, Jos
AU - Ramms, Anne S.
AU - Wild, Raphael
AU - Hammer, Julia
AU - Merkel, Melanie
AU - Derenbach, Laura
AU - Préau, Laetitia
AU - Hinkel, Rabea
AU - Suarez-Martinez, Irina
AU - Schulte-Merker, Stefan
AU - Vidal, Ramon
AU - Sauer, Sascha
AU - Kivelä, Riikka
AU - Alitalo, Kari
AU - Kupatt, Christian
AU - van Buul, Jaap D.
AU - le Noble, Ferdinand
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85093069460&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-19008-0
DO - 10.1038/s41467-020-19008-0
M3 - Article
C2 - 33087700
AN - SCOPUS:85093069460
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5319
ER -