TY  - JOUR
A1  - Renz, Marc
A1  - Otten, Cecile
A1  - Faurobert, Eva
A1  - Rudolph, Franziska
A1  - Zhu, Yuan
A1  - Boulday, Gwenola
A1  - Duchene, Johan
A1  - Mickoleit, Michaela
A1  - Dietrich, Ann-Christin
A1  - Ramspacher, Caroline
A1  - Steed, Emily
A1  - Manet-Dupe, Sandra
A1  - Benz, Alexander
A1  - Hassel, David
A1  - Vermot, Julien
A1  - Huisken, Jan
A1  - Tournier-Lasserve, Elisabeth
A1  - Felbor, Ute
A1  - Sure, Ulrich
A1  - Albiges-Rizo, Corinne
A1  - Abdelilah-Seyfried, Salim
T1  - Regulation of beta 1 Integrin-Klf2-Mediated angiogenesis by CCM proteins
JF  - Developmental cell
N2  - Mechanotransduction pathways are activated in response to biophysical stimuli during the development or homeostasis of organs and tissues. In zebrafish, the blood-flow-sensitive transcription factor Klf2a promotes VEGF-dependent angiogenesis. However, the means by which the Klf2a mechanotransduction pathway is regulated to prevent continuous angiogenesis remain unknown. Here we report that the upregulation of klf2 mRNA causes enhanced egfl7 expression and angiogenesis signaling, which underlies cardiovascular defects associated with the loss of cerebral cavernous malformation (CCM) proteins in the zebrafish embryo. Using CCM-protein-depleted human umbilical vein endothelial cells, we show that the misexpression of KLF2 mRNA requires the extracellular matrix-binding receptor beta 1 integrin and occurs in the absence of blood flow. Downregulation of beta 1 integrin rescues ccm mutant cardiovascular malformations in zebrafish. Our work reveals a beta 1 integrin-Klf2-Egfl7-signaling pathway that is tightly regulated by CCM proteins. This regulation prevents angiogenic overgrowth and ensures the quiescence of endothelial cells.
Y1  - 2015
U6  - https://doi.org/10.1016/j.devcel.2014.12.016
SN  - 1534-5807
SN  - 1878-1551
VL  - 32
IS  - 2
SP  - 181
EP  - 190
PB  - Cell Press
CY  - Cambridge
ER  -