Neuritin (Nrn1 or cpg15) is a GPI-anchored protein acting in a non-cell autonomous manner to coordinately regulate growth of apposing dendritic and axonal arbors, and to promote synaptic maturation. Interestingly, Nrn1 expression peaks during neuronal development in embryonic proliferative zonescharacterized by an active neuronal migration.

We investigated whether Nrn1 regulates neuronal migration utilizing two similar cell lines, that have a different migratory behavior: Gn11 cells (migrating neurons) and GT1-7 cells (non migrating neurons), and analysed Nrn1 mRNA and protein expression levels. Interestingly, Nrn1 expression is much higher in migrating Gn11 neurons than in non-migrating GT1-7 neurons. In Boyden microchemotaxisand wound-healing assays, the migratory ability of Gn11 neurons is reduced when Nrn1 expression is silenced, while it is increased when Nrn1 is over-expressed. ICC and Western blot analyses of post-translational modifications of tubulin known to be associated with differently dynamic microtubules show an enrichment of stable microtubules in Nrn1 silenced neurons that likely reflects the diminished migratory capability of the cells.

These results demonstrate that the migratory properties of Gn11 cells may be altered by modulating Nrn1 levels and strongly suggest, for the first time, that Nrn1 is a regulator of neuronal migration.

(Grants: Telethon; Italian Ministry of Labour, Health and Social Affairs; Fondazione Cariplo)