The aquatic invertebrate Hydra vulgaris releases molecular messages through extracellular vesicles
Recent body of evidence demonstrates that extracellular vesicles (EVs) represent the first language of cell-cell communication emerged during evolution. In aquatic environments, transferring signals between cells by EVs offers protection against degradation, allowing delivering of chemical information in high local concentrations to the target cells. The packaging of multiple signals, including those of hydrophobic nature, ensures target cells to receive the same EV-conveyed messages, and the coordination of a variety of physiological processes across cells of a single organisms, or at the population level, i.e., mediating the population's response to changing environmental conditions. Here, we purified EVs from the medium of the freshwater invertebrate Hydra vulgaris, and the molecular profiling by proteomic and transcriptomic analyses revealed multiple markers of the exosome EV subtype, from structural proteins to stress induced messages promoting cell survival. Moreover, positive and negative regulators of the Wnt/β-catenin signaling pathway, the major developmental pathway acting in body axial patterning, were identified. Functional analysis on amputated polyps revealed EV ability to modulate both head and foot regeneration, suggesting bioactivity of the EV cargo and opening new perspectives on the mechanisms of developmental signalling. Our results open the path to unravel EV biogenesis and function in all cnidarian species, tracing back the origin of the cell-cell, cross-species or cross-kingdom communication in aquatic ecosystems. ; Proteomic analyses were performed in the Proteomics Platform of Servicios Científico Técnicos del CIBA (IACS-Universidad de Zaragoza), ProteoRed ISCIII member. RNA-seq analyses were performed by Sequentia Biotech S.L. (Barcelona, Spain). The authors acknowledge Mario Isas, Keck School of Medicine of USC Los Angeles, CA, for the kind gift of anti Hydra annexin B12 antibody. GT thanks the MIUR project SHARID-ARS01-01270 for financial support. MMo acknowledges financial support from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant Agreement No 853468), from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 660228 and from the Spanish Ministry of Science and Innovation through the Ramón y Cajal grant RyC 2019-026860-I. ; Peer reviewed