2014/12/09

Exosomes participate in the Hedgehog gradient formation required in development

Tissue and organ formation require a tight concerted coordination of many different cell types that have to proliferate and differentiate in the right place and moment. For proper development, the organism establishes a spatio-temporal expression of special type of molecules called morphogens that, by creating a dynamic gradient concentration in time and space, are able to dictate the final fate of the cells within a morphogenetic field. Hedgehog protein is one of these morphogens that has been implicated in development, adult stem cell maintenance, cell migration, and axon guidance in a wide range of organisms. In addition, aberrant activation of Hh signaling pathway has been implicated in many types of human cancers. The work conducted by Dr. Isabel Guerrero (CBM-SO, Madrid) and Juan Manuel Falcon-Perez (CIC bioGUNE, Derio) has shown that the Hedgehog protein travels into small vesicles named exosomes. These type of vesicles secreted by most of the cells of the body have received great attention by the scientific community thanks to their potential as disease biomarkers and their role as intercellular communicators regulating proliferation, differentiation and migration in many biological and pathological processes. Using Drosophila in vivo and in vitro models, this work demonstrates that the Hedgehog protein is associated to exosomes, and that interference with the biogenesis of exosomes affects the proper Hedgehog gradient formation, supporting these vesicles as important players in development. The work has been published this month in Nature Communications (Gradilla, González et al., 2014) and has also counted with the important participation of the groups of Rosa Barrio (CIC bioGUNE) and Marcus Bischoff (University of St. Andrews, Scotland, UK).