mRNA localisation in endothelial cells regulates blood vessel sprouting

2018 
The subcellular distribution of mRNAs is a fundamental biological mechanism implicated in the spatial regulation of gene expression in many cellular contexts. However, whether mRNA localisation contributes to complex morphogenetic processes underpinning tissue development remains unknown. We focused on a model transcript, RAB13, and demonstrated how it is preferentially localised to and locally translated at the leading edge of migrating endothelial cells. We generated a novel MS2-GFPnls zebrafish reporter strain and use the 3′ UTR of RAB13 to show, for the first time, tissue-specific visualisation of a localised RNA in migratory cell processes in a living vertebrate organism. Moreover, after mutating the endogenous 3′ UTR of RAB13 to disrupt transcript localisation in-vivo, we report altered formation of endothelial cell protrusions within sprouting vessels. Hence, we demonstrate the involvement of mRNA localisation in endothelial cell migration during angiogenesis and are the first to reveal that subcellular transcript distribution modulates tissue morphogenesis.
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