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SRF selectively controls tip cell invasive behavior in angiogenesis

Item Type:Article
Title:SRF selectively controls tip cell invasive behavior in angiogenesis
Creators Name:Franco, C.A. and Blanc, J. and Parlakian, A. and Blanco, R. and Aspalter, I.M. and Kazakova, N. and Diguet, N. and Mylonas, E. and Gao-Li, J. and Vaahtokari, A. and Penard-Lacronique, V. and Fruttiger, M. and Rosewell, I. and Mericskay, M. and Gerhardt, H. and Li, Z.
Abstract:Efficient angiogenic sprouting is essential for embryonic, postnatal and tumor development. Serum response factor (SRF) is known to be important for embryonic vascular development. Here, we studied the effect of inducible endothelial-specific deletion of Srf in postnatal and adult mice. We find that endothelial SRF activity is vital for postnatal growth and survival, and is equally required for developmental and pathological angiogenesis, including during tumor growth. Our results demonstrate that SRF is selectively required for endothelial filopodia formation and cell contractility during sprouting angiogenesis, but seems dispensable for vascular remodeling. At the molecular level, we observe that vascular endothelial growth factor A induces nuclear accumulation of myocardin-related transcription factors (MRTFs) and regulates MRTF/SRF-dependent target genes including Myl9, which is important for endothelial cell migration in vitro. We conclude that SRF has a unique function in regulating migratory tip cell behavior during sprouting angiogenesis. We hypothesize that targeting the SRF pathway could provide an opportunity to selectively target tip cell filopodia-driven angiogenesis to restrict tumor growth.
Keywords:Filopodia, SRF, Sprouting Angiogenesis, Actin, Myosin, Animals, Mouse
Source:Development
ISSN:0950-1991
Publisher:Company of Biologists (U.K.)
Volume:140
Number:11
Page Range:2321-2333
Date:June 2013
Official Publication:https://doi.org/10.1242/dev.091074
PubMed:View item in PubMed

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