miR-150 controls developmental angiogenesis via ribosome biogenesis-dependent regulation of Notch signaling

Abstract

The development of a functional vasculature is controlled by the coordination of various mechanisms. Key molecules and signaling pathways regulating vascular development remain far from understood. Here, we demonstrate that miR-150 is highly enriched in zebrafish vascular endothelial cells (ECs), and plays a key role in regulating developmental angiogenesis during embryogenesis. Depletion of miR-150 impairs intersegmental vessel (ISV) sprouting, whereas EC-overexpression of miR-150 induces ectopic vascular sprouting. Mechanistically, miR-150 binds to the 3’UTR of zebrafish wdr75 to modulate ribosome biogenesis. Loss of miR-150 led to upregulated ribosome biogenesis, which enhanced Notch signaling activity and inhibited developmental angiogenesis. Pharmacological inhibition of ribosome biogenesis or Notch signaling effectively rescued the angiogenic defects in miR-150-deficient embryos. These findings establish miR-150 as a key regulator of developmental angiogenesis through modulation of ribosome biogenesis and downstream Notch signaling during zebrafish embryogenesis.