UCSF

Neural crest cells, a multipotent vertebrate stem cell population, undergo a tightly regulated epithelial-mesenchymal transition (EMT) to delaminate from the neural tube and initiate migration. Neural crest EMT is controlled by a transient pulse of Draxin, which acts as a molecular rheostat of canonical Wnt signaling, and is then rapidly downregulated by unknown mechanisms. To address this, here we use in vivo reporter assays and live RNA imaging to show that Draxin mRNA is rapidly degraded posttranscriptionally via its 3' untranslated region. We found that Draxin transcripts are targeted to cytoplasmic processing bodies (P-bodies), which are membrane-less sites of RNA processing and decay. Disruption of P-bodies by CRISPR/Cas9-mediated depletion of the RNA helicase DDX6 prevented posttranscriptional downregulation of Draxin and impaired neural crest EMT in vivo. These findings parallel observations in human patients carrying DDX6 mutations, who exhibit defects in P-body assembly and craniofacial abnormalities associated with neural crest dysfunction. Together, our results identify P-bodies as regulators of Draxin mRNA decay and reveal a spatially organized mechanism of RNA turnover that controls neural crest EMT during vertebrate development.