We suggest a model in which DS-epi1 converts selected GlcA residues into isolated IdoA on CS/DS PGs in Xenopus CNC cells (Fig. 8). Following interaction with fibronectin, CS/DS PGs lead to the rearrangement of the actin cytoskeleton and facilitate CNC cell adhesion and migration. In support of this model, we demonstrated in Xenopus CNC that (1) DS-epi1 is expressed and synthesizes IdoA on CS/DS-PGs, (2) DS-epi1 has a tissue-autonomous role in cell migration, and (3) DS-epi1 is required for the cells to adhere, spread and extend polarized cell processes on fibronectin. The integrin α5β1 heterodimer (Alfandari et al., 2003) and Sdc4 (Woods et al., 2000; Matthews et al., 2008) bind to distinct domains of fibronectin and are required for NC cell adhesion and migration. The interaction of GAG chains with fibronectin is crucial for the functions of integrin α5β1 in cell migration (Shworak et al., 1994) and Sdc4 in the proper organization of the actin cytoskeleton and cell adhesion (Gopal et al., 2010). Although co-expressed with Dse in the CNC at the onset of cell migration, Itga5, Itgb1 and Sdc4
