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Vascular endothelial cells (ECs) in angiogenesis exhibit inhomogeneous collective migration called "cell mixing", in which cells change their relative positions by overtaking each other. However, how such complex EC dynamics lead to the formation of highly ordered branching structures remains largely unknown. To uncover hidden laws of integration driving angiogenic morphogenesis, we analyzed EC behaviors in an in vitro angiogenic sprouting assay using mouse aortic explants in combination with mathematical modeling. Time-lapse imaging of sprouts extended from EC sheets around tissue explants showed directional cohesive EC movements with frequent U-turns, which often coupled with tip cell overtaking. Imaging of isolated branches deprived of basal cell sheets revealed a requirement of a constant supply of immigrating cells for ECs to branch forward. Anisotropic attractive forces between neighboring cells passing each other were likely to underlie these EC motility patterns, as evidenced by an experimentally validated mathematical model. These results suggest that cohesive movements with anisotropic cell-to-cell interactions characterize the EC motility, which may drive branch elongation depending on a constant cell supply. The present findings provide novel insights into a cell motility-based understanding of angiogenic morphogenesis.

The shallow oxidized asthenosphere may contain a small fraction of potassic silicate melts that are enriched in incompatible trace elements and volatiles. Here, to determine the chemical composition of such melt, we analysed fossilized melt inclusions, preserved as multiphase solid inclusions, from an orogenic garnet peridotite in the Bohemian Massif. Garnet-poor (2 vol.%) peridotite preserves inclusions of carbonated potassic silicate melt within Zn-poor chromite (<400 ppm) in the clinopyroxene-free harzburgite assemblage that equilibrated within the hot mantle wedge (Stage 1, > 1180 °C at 3 GPa). The carbonated potassic silicate melt, which has a major element oxide chemical composition of K 2 O = 5.2 wt.%, CaO = 17 wt.%, MgO = 18 wt.%, CO 2  = 22 wt.%, and SiO 2  = 20 wt.%, contains extremely high concentrations of large ion lithophile elements, similar to kimberlite melts. Peridotites cooled down to ≅800 °C during Stage 2, resulted in the growth of garnet relatively poor in pyrope content, molar Mg/(Mg + Fe + Ca + Mn), (ca. 67 mol.%). This garnet displays a sinusoidal REE pattern that formed in equilibrium with carbonatitic fluid. Subsequently, subduction of the peridotite resulted in the formation of garnet with a slightly higher pyrope content (70 mol.%) during the Variscan subduction Stage 3 (950 °C, 2.9 GPa). These data suggest the following scenario for the generation of melt in the mantle wedge. Primarily, infiltration of sediment-derived potassic carbonatite melt into the deep mantle wedge resulted in the growth of phlogopite and carbonate/diamond. Formation of volatile-bearing minerals lowered the density and strength of the peridotite. Finally, phlogopite-bearing carbonated peridotite rose as diapirs in the mantle wedge to form carbonated potassic silicate melts at the base of the overriding lithosphere.