SUMMARY
The subcellular targeting of mRNAs is fundamental to the spatial regulation of gene expression. However, whether mRNA localization directs complex morphogenetic events underpinning tissue development remains unknown. Here we reveal that spatial modulation of transcripts defines a novel paradigm for directional control of tissue movement and morphogenesis. Focusing on angiogenesis as a morphogenetic model, we identify RAB13 as a key vascular transcript targeted and locally translated at the leading edge of migrating endothelial cells. We define the 3’UTR “zipcode” driving RAB13 targeting and use novel vascular-specific MS2-MCP RNA-labelling tools in zebrafish to uniquely reveal the precise spatiotemporal dynamics of RNA localization in migratory cell processes in-vivo. Moreover, mutation of the endogenous zebrafish rab13 3’UTR disrupts transcript localization and perturbs endothelial cell protrusion dynamics during angiogenesis. Hence, local mRNA targeting imparts key spatial information on developing tissues, suggesting broad roles in the directional control of tissue formation in health and disease.
