RT Journal Article SR Electronic T1 Microvilli-derived Extracellular Vesicles Govern Morphogenesis in Drosophila wing epithelium JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.01.363697 DO 10.1101/2020.11.01.363697 A1 Ilse Hurbain A1 Anne-Sophie Macé A1 Maryse Romao A1 Lucie Sengmanivong A1 Laurent Ruel A1 Renata Basto A1 Pascal P. Thérond A1 Graça Raposo A1 Gisela D’Angelo YR 2020 UL http://biorxiv.org/content/early/2020/11/02/2020.11.01.363697.abstract AB The regulation and coordination of developmental processes involves the secretion of morphogens and membrane carriers, including extracellular vesicles, which facilitate their transport over long distance. The long-range activity of the Hedgehog morphogen is conveyed by extracellular vesicles. However, the site and the molecular basis of their biogenesis remains unknown. By combining fluorescence and electron microscopy combined with genetics and cell biology approaches, we investigated the origin and the cellular mechanisms underlying extracellular vesicle biogenesis, and their contribution to Drosophila wing disc development, exploiting Hedgehog as a long-range morphogen. We show that microvilli of Drosophila wing disc epithelium are the site of generation of small extracellular vesicles that transport Hedgehog across the tissue. This process requires the Prominin-like protein, whose activity, together with interacting cytoskeleton components and lipids, is critical for maintaining microvilli integrity and function in secretion. Our results provide the first evidence that microvilli-derived extracellular vesicles contribute to Hedgehog long-range signaling activity highlighting their physiological significance in tissue development in vivo.Competing Interest StatementThe authors have declared no competing interest.