(The) role of Sox F transcription factors during vascular development

Abstract

VEGF is a key signaling for angiogenesis requiring exquisite regulation. While Notch pathway suppresses excessive VEGF activity by negative feedback, positive feedback control for augmenting VEGF signaling has not been revealed. How VEGF signaling is engaged with transcriptional regulation is also poorly understood. Here, we explored how SoxF transcription factors Sox7 and Sox17 are involved in VEGF signaling in mouse developmental angiogenesis. Sox7 is expressed specifically in endothelial cells and its deletion reduced angiogenesis, exhibiting a substantial overlap with Sox17 in expression and function. Compound heterozygosity of Sox7 and Sox17 phenocopied vascular defects by either Sox7 or Sox17 homozygous knockout, indicating genetic cooperation of Sox7 and Sox17. VEGF upregulated Sox7 and Sox17 coincidently in angiogenic contexts, and in turn Sox7 and Sox17 promote VEGFR2 expression, creating a positive feedback loop. We identified SoxF transcription factors as positive feedback regulators for reinforcing VEGF signaling and indispensable players for developmental angiogenesis.