SRF selectively controls tip cell invasive behavior in angiogenesis

Claudio A. Franco, Jocelyne Blanc, Ara Parlakian, Raquel Blanco, Irene M. Aspalter, Natalia Kazakova, Nicolas Diguet, Elena Mylonas, Jacqueline Gao-Li, Anne Vaahtokari, Virgine Penard-Lacronique, Markus Fruttiger, Ian Rosewell, Mathias Mericskay, Holger Gerhardt, Zhenlin Li

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

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 myocardinrelated 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.

Original languageEnglish
Pages (from-to)2321-2333
Number of pages13
JournalDevelopment (Cambridge)
Volume140
Issue number11
DOIs
Publication statusPublished - 1 Jun 2012
Externally publishedYes

Keywords

  • Actin
  • Filopodia
  • Mouse
  • Myosin
  • Sprouting angiogenesis
  • SRF

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