Schematic representation of miR-27b functions. (A) Regulation of vascular sprouting. At low levels, miR-27b allows the expression of Spry2 and Dll4, which block capillary branching and tip endothelial cell fate, respectively. In addition, miR-27 down-regulates Flt1, possibly via Dll4/Notch. Flt1 also represses tip endothelial cell fate and therefore vascular sprouting. When miR-27b levels are high, Spry2, Dll4, and Flt1 are low and allow for the increased occurrence of the tip cells and therefore denser capillaries. (B) Regulation of venous specification. In endothelial cells of the early DA, miR-27b blocks Dll4 expression. Consequently, Notch signaling weakens, causing lower EfnB2 expression, whereas the venous marker EphB4 increases. At the same time, the repression of Spry2 releases EphB4 expression and lowers Flt4. The net result is a sum of increased venous markers, decreased expression of arterial genes, and accelerated venous differentiation.