Citation:
bioRxiv. 2018. doi:10.1101/321356
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.
Epub:
Not Epub
Link to Publication:
https://www.biorxiv.org/content/early/2018/05/13/321356
Organism or Cell Type:
zebrafish
Delivery Method:
microinjection