Oligodendrocyte precursor migration and differentiation: Combined effects of PSA residues, growth factors, and substrates

Using the oligosphere strategy (V, Avellana-Adalid et al., 1996, J, Neurosc i, Res. 45, 558-570), we compared the migratory behavior of oligodendrocyte preprogenitors (OPP) that expressed the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) and of GD3-positive oligodendrocyte proge nitors (OP). To study the role of PSA in OPP migration, we used endoneurami nidase-N, which specifically cleaves PSA from NCAM. Kinetic data showed tha t (i) migration velocity decreased with time and was favored on polyornithi ne compared to Matrigel; (ii) cells emerging from spheres enriched in PSA-N CAMC OPP migrated farther than those from spheres enriched in GD3(+) OF, th eir migration being enhanced by the addition of growth factors; (iii) remov al of PSA from NCAM moderately reduced OPP migration and induced their diff erentiation in GD3(+) OP and GFAP(+) astrocytes; (iv) blocking integrins re duced their migration, suggesting an alternative mechanism of migration. Al together these data illustrate that motility and differentiation of OPP inv olve the combinatorial action of PSA-NCAM, molecules of the ECM and their r eceptors, and growth factors.