Figure 2.

Tip cell phenotype expression in response to angiogenic cues in endothelial cells at the vasculogenesis frontier. In endothelial cells at the angiogenesis frontier during vascular development, JunB expression is induced by angiogenic cues including hypoxia and vascular endothelial growth factor A (VEGFA) through hypoxia-inducible factor 1 subunit alpha (HIF1α) or phosphorylation of protein kinase C theta (PKCθ). “P” indicates phosphorylation of the molecule. (left). In the developing skin vasculatures, the direct interaction of endothelial cells with peripheral neurons can also stimulate JunB expression and coordinate neurovascular parallel alignment (left). In tip cells, JunB is involved in the upregulation of vascular endothelial growth factor receptor 3 (VEGFR3) expression which is a key VEGFR for angiogenesis at specific developmental stages. VEGFR3 binds vascular endothelial growth factor C and D (VEGFC/D), while signaling cascades are required for tip cell migration and sprouting of endothelial cells by signal transducer and activator of transcription 3 (STAT3) activation at the angiogenic frontier (right). The arrows indicate the relationship of signaling directions.