SRF selectively controls tip cell invasive behavior in angiogenesis.

TitleSRF selectively controls tip cell invasive behavior in angiogenesis.
Publication TypeJournal Article
Year of Publication2013
AuthorsFranco CA, Blanc J, Parlakian A, Blanco R, Aspalter IM, Kazakova N, Diguet N, Mylonas E, Gao-Li J, Vaahtokari A, Penard-Lacronique V, Fruttiger M, Rosewell I, Mericskay M, Gerhardt H, Li Z
JournalDevelopment (Cambridge, England)
Volume140
Issue11
Pagination2321-33
Date Published2013 Jun
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.

DOI10.1371/journal.pone.0063013
Alternate JournalDevelopment