Live tracking of inter-organ communication by endogenous exosomes in vivo
Our recent works aim at understanding the conserved mechanisms that regulate the balance between lysosomal degradation and exosomes secretion and to unveil the biology of extracellular vesicles in vivo. Extracellular vesicles (EVs) such as exosomes are released by most cell types but the definitive demonstration of their functional relevance remains challenging due to the lack of appropriate model organisms. Here we developed an in vivo model to study EV physiology by expressing CD63-pHluorin in zebrafish embryos. A combination of microscopy techniques and proteomic analysis allowed us to study the biogenesis, composition, transfer, uptake and fate of individual endogenous EVs in vivo. We identified an exosome population released in a syntenin-dependent manner from the Yolk Syncytial Layer into the blood circulation. These exosomes were captured, endocytosed and degraded by patrolling macrophages and endothelial cells in the Caudal Vein Plexus (CVP) in a scavenger receptor and dynamin-dependent manner. Interference with exosome secretion and uptake affected CVP growth, supporting their trophic role. Altogether, our work provides a unique model to track in vivo inter-organ communication by endogenous exosomes at individual vesicle level with high spatio-temporal accuracy.
Research Director CNRS, Team leader Endosomal dynamic in neuropathies - Center of Psychiatry and Neurosciences - U-894 INSERM
Domain 4 - UMR 144 - Subcellular Structure and Cellular Dynamics