The evolutionarily conserved transcription factor SRF (serum response factor) is involved in several developmental processes that require cell migration, including embryonic angiogenesis. Here (p. ), Zhenlin Li and colleagues investigate the function of SRF during postnatal angiogenesis. They show that the inducible, endothelial-specific deletion of Srf in postnatal mice reduces postnatal growth and viability, induces systemic hypovascularisation and retinal angiopathy, and decreases angiogenesis in implanted tumours. Genetic mosaic analysis indicates that defective filopodia formation by the tip cells of angiogenic sprouts and reduced cell contractility are the primary causes of these angiogenic defects. The researchers also show that VEGFA induces nuclear accumulation of myocardin-related transcription factors (MRTFs; co-factors that regulate the transcriptional output of SRF) and that MRTF-SRF activity controls the expression of contractility genes that are important for endothelial cell migration. The researchers conclude that SRF regulates tip cell invasive behaviour during sprouting angiogenesis and hypothesize that curbing pathological angiogenesis by targeting the SRF pathway might restrict tumour growth.
