Hosted by the School of Biochemistry
During angiogenesis, endothelial cells engage in coordinated and complex migration events to form new blood vessels from parental vasculature. Great advances in angiogenesis research have mainly uncovered protein roles involved in mechanisms of vessel formation, from cell adhesion and signalling to transcriptional regulation. However, while the subcellular localisation of mRNAs is a well-established step between gene transcription and protein activity, whether this mechanism controls angiogenesis had never been addressed. Thus, we set out to investigate the cytoplasmic distribution of mRNAs in migratory endothelial cells and their roles in vessel formation. Amongst the RNAs isolated from protrusions, we found transcripts encoding proteins implicated in cell motility and cytoskeletal dynamics. Using a reporter system, we dissected cis-regulatory elements within the localised mRNAs responsible for their transport. We complemented these in vitro assays with live imaging of vascular-specific MS2 transgenic zebrafish embryos, and confirmed that mRNAs are indeed localised to endothelial cell protrusions during developmental angiogenesis. To understand the functional implications of such phenomenon, we excised the localisation elements from endogenous transcripts, both in vitro and in vivo. These experiments showed that correct mRNA localisation underpins endothelial cell morphology and behaviour during angiogenesis. In summary, we are now unveiling the fascinating implications of subcellular mRNA distribution in blood vessel formation, which can pave the way for the development of therapies to treat pathological neovascularisation.