Figure 12. A schematic representation of endothelial Ca²⁺ responses during sprouting angiogenesis from the DA.

Ca²⁺ oscillations occur widely within the DA before ISV sprouting. Dll4/Notch signaling attenuates Ca²⁺ responses in the entire DA at this stage. Ca²⁺ oscillations are restricted to single or two neighboring ECs just after vessel sprouting and then further restricted to single ECs that eventually become tip cells. Dll4/Notch signaling is required for the selection of single tip cells. During stalk cell budding, tip cells and stalk cells exhibit Ca²⁺ oscillations, although the Ca²⁺-oscillatory activity in stalk cells is weaker than that in tip cells. Dll4/Notch signaling regulates the selection of single stalk cells. After stalk cells completely come out from the DA, strong Ca²⁺ oscillations occur both in tip cells and stalk cells. Intensity of green reflects the frequency of Ca²⁺ oscillations. DA, dorsal aorta.

DOI: http://dx.doi.org/10.7554/eLife.08817.036