Changes in RNA stability drive neural crest development in vivo

Neural crest cells are an essential, multipotent stem cell population in the vertebrate embryo. During development, neural crest cells undergo a tightly regulated epithelial-to-mesenchymal transition (EMT) to delaminate from the neural tube and initiate migration to populate diverse embryonic tissues. We have shown that avian cranial neural crest development is controlled by a transient pulse of Draxin, which acts as a molecular rheostat of canonical Wnt signaling. Tight regulation of Draxin expression is essential for proper cranial neural crest development, and its rapid downregulation is a hallmark of EMT. However, precisely how Draxin transcripts are regulated to ensure their rapid removal is unclear. To tackle this question, we adapted in vivo reporters and a live RNA imaging approach and found that Draxin mRNA localizes for decay to processing bodies (P-bodies), cytoplasmic granules involved in RNA turnover and storage. P-body disruption abrogated Draxin mRNA degradation, and subsequently caused defects in cranial neural crest migration. This is consistent with observations in human patients who display defects in P-body assembly and often present with craniofacial abnormalities, a hallmark of neural crest dysfunction. To parse the mechanisms underlying the transition of Draxin mRNA stability to decay, we analyzed premigratory cranial neural crest single cell-RNA sequencing data and identified an RNA-binding protein, Elavl1, that targets Draxin mRNA. Downregulation of Elavl1 in cranial neural crest prematurely destabilized Draxin mRNA and altered specification. Together, our data highlight a novel and important role for post-transcriptional regulation in neural crest— balancing transcript stability and decay to control cell fate choices.