We note that despite the misregulation of NC-specific transcription factors, NC cells are formed in DS-epi1-deficient embryos. This finding is exemplified by the expression of Twist, which is initially reduced likely because of the concomitant downregulation of Foxd3 expression (Sasai et al., 2001), but is subsequently restored in CNC cells at the post-neurula stage, possibly as a result of Wnt/β-catenin signaling, which induces NC cell fate and maintains Twist expression during migration (Chang and Hemmati-Brivanlou, 1998; Borchers et al., 2001). The downregulation of Twist and Foxd3 expression in DS-epi1-morphant neurula embryos supports a function of DS-epi1 in EMT. Twist is a repressor of E-cadherin in Xenopus NC cells (Barriga et al., 2013). Low Twist and high E-cadherin cause a loss of polarized protrusions and a failure of cell–cell dissociation (Scarpa et al., 2015). Foxd3 promotes the EMT by modulating cell–cell adhesion in the chick embryo (Cheung et al., 2005; Fairchild et al., 2014). EMT inhibition might also explain the impaired segregation and reduced ventral migration of CNC cell streams following the knockdown of DS-epi-1.
