To investigate the function of IdoA in CS/DS chains at the cellular level, we searched for an appropriate model system. Craniofacial anomalies constitute a high proportion of congenital malformations and are mainly caused by neural crest (NC) development defects (Gorlin et al., 1990). Interestingly, the craniofacial features in MCEDS (Müller et al., 2013; Syx et al., 2015; Kosho, 2016) are reminiscent of NC-associated disorders, such as Treacher Collins syndrome, Nager syndrome and Miller syndrome (Trainor and Andrews, 2013), which indicates that the NC might be a suitable model system for MCEDS. The NC comprises a population of multipotent and highly migratory cells that form at the border between the neural and epidermal ectoderm in the vertebrate embryo (Mayor and Theveneau, 2013; Simões-Costa and Bronner, 2015). Research predominately in Xenopus and the chick embryo has demonstrated that signaling molecules secreted from the surrounding ectoderm and the underlying mesoderm, including bone morphogenetic proteins, Wnts and fibroblast growth factors (FGFs), orchestrate a combinatorial expression of transcription factors that drive NC specification and morphogenesis. NC cells undergo an epithelial–mesenchymal transition (EMT), migrate along restricted
