Modulation of cell-cell adhesion is crucial for regulating neuronal migration and maintenance of structural plasticity in the embryonic and mature brain. Such modulation can be obtained by the enzymatic attachment of polysialic acid (PSA) to the neural cell adhesion molecule (NCAM) by means of the polysialyltransferases STX and PST. Thus, differential expression of STX and PST is likely to be responsible for varying functions of PSA-NCAM during neuronal differentiation, maintenance, plasticity, and regeneration. We have isolated the zebrafish homologues of STX (St8sia2) and PST (St8sia4) and demonstrate that their expression in the embryonic and adult nervous system is often confined to regions of neuronal migration. Moreover, in the adult cerebellum, the complementary expression pattern of both polysialyltransferases suggests a function in regulating cerebellar neuronal plasticity. Enzymatic removal of PSA in the embryonic cerebellum results in impaired neuronal migration, suggesting that PSA-NCAM is a key regulator of motility for cerebellar neuronal progenitors.