As a result of their large embryo size and external development, Xenopus is a favorable experimental system. Here, we demonstrate that DS-epi1 accounts for most DS biosynthesis in the early Xenopus embryo. In loss-of-function assays, DS-epi1 is required for the correct regulation of neural-plate-border- and NC-specific transcription factors. Moreover, DS-epi1 has an intrinsic role in NC cell migration and is indispensable for the cell adhesion, spreading and formation of polarized cell structures on fibronectin. Human DSE expression correlates with genetic markers of EMT, invasion and metastasis in both neuroblastoma and melanoma, which suggests a potential role of DS-epi1 in NC-derived cancers. A model is proposed, in which CS/DS PGs mediate the adherence of NC cells to fibronectin during cell migration.
