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Document Version Version Comment Date Status
717956.0 Automatic journal name synchronization 16.04.2016 20:15 Released

ID: 717956.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2015 (arch)
Regulation of β1 Integrin-Klf2-Mediated Angiogenesis by CCM Proteins.
Authors:Renz, Marc; Otten, Cécile; Faurobert, Eva; Rudolph, Franziska; Zhu, Yu; Boulday, Gwénola; Duchene, Johan; Mickoleit, Michaela; Dietrich, Ann-Christin; Ramspacher, Caroline; Steed, Emily; Manet-Dupé, Sandra; Benz, Alexander; Hassel, David; Vermot, Julien; Huisken, Jan; Tournier-Lasserve, Elisabeth; Felbor, Ute; Sure, Ulrich; Albiges-Rizo, Corinne; Abdelilah-Seyfried, Salim
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Developmental Cell
Issue / Number:2
Start Page:181
End Page:190
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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 β1 integrin and occurs in the absence of blood flow. Downregulation of β1 integrin rescues ccm mutant cardiovascular malformations in zebrafish. Our work reveals a β1 integrin-Klf2-Egfl7-signaling pathway that is tightly regulated by CCM proteins. This regulation prevents angiogenic overgrowth and ensures the quiescence of endothelial cells.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Thüm
Affiliations:MPI für molekulare Zellbiologie und Genetik