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bioRxiv · 10.1101/321356

Extracellular Vesicle-delivered Bone Morphogenetic Proteins: A novel paracrine mechanism during embryonic development

Draebing, T.·Heigwer, J.·Juergensen, L.·Katus, H. A.·Hassel, D.
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Abstract

Morphogens including Wnt, Hedgehog and BMP proteins are essential during embryonic development and early induction of organ progenitors. Besides free diffusion to form signalling gradients, extracellular vesicle- (EV-) mediated morphogen transport was identified as a central mechanism for Wnt- and Hh-signalling. Here, we investigated EVs isolated from whole zebrafish embryos as a potential morphogen transport mechanism. Inhibition of EV-secretion during development leads to severe dorsalization phenotypes, reminiscent of disrupted BMP-signalling. Subsequently, we found that EVs isolated from zebrafish embryos at bud stage contain biologically active BMP2/4 protein. Embryos with inhibited EV secretion display reduced Smad1/5/9-phosphorylation and downstream gene expression activity. We further show that BMP-containing EVs are secreted by endodermal cells in vitro, and inhibition of endodermal-EV release in vivo causes signs of BMP signalling loss. Our data provides evidence that establishes the transport of BMP2/4 by EVs as an essential but so far undiscovered mechanism in developmental morphogenesis.

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Draebing, T., Heigwer, J., Juergensen, L., Katus, H. A., Hassel, D.. 2018-05-14. Extracellular Vesicle-delivered Bone Morphogenetic Proteins: A novel paracrine mechanism during embryonic development. https://doi.org/10.1101/321356

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