MCEDS is the first disorder that has been discovered to specifically affect the biosynthesis of DS (Kosho et al., 2016). A defect in NC cells might contribute to the craniofacial phenotype in this condition. The features of MCEDS include hypoplasia of the jaw, high and/or cleft palate, midface skeletal anomaly, down-slanting palpedral fissues and malformed ears (Müller et al., 2013; Syx et al., 2015). These craniofacial anomalies also occur in congenital defects caused by a reduced amount or abnormal migration of NC cells into the first (mandibular) and second (hyoid) pharyngeal arch in Treacher Collins syndrome, Nager syndrome and Miller syndrome (Trainor and Andrews, 2013), which suggests a conserved role of DS in human NC development. The knockdown of DS-epi1 in Xenopus embryos phenocopies the craniofacial defects in humans. Our study in the Xenopus model suggests that an insufficient amount of NC cells migrating to their destinations might be a result of (1) a defect in the EMT, (2) an inability of NC cells to adhere to fibronectin, and (3) cell death as a consequence of anchorage loss of NC
