Glial cells of the O-2A lineage bind preferentially to N-cadherin and develop distinct morphologies

Environmental cues guiding glial cell behavior during development or regeneration of the nervous system are provided by both soluble and nondiffusible factors. We examined the influences of purified extracellular matrix molecules and cell adhesion molecules on the development and proliferation of glial cells from neonatal rat optic nerves. Dissociated optic nerve glia were plated on fibronectin, laminin, collagen type IV, L1, N-cadherin, and N-CAM. Cultures were grown in chemically defined medium to promote formation of oligodendrocytes. Other cultures were grown in 10% serum to support type-1 astrocytes and the differentiation of O-2A progenitor cells to type-2 astrocytes. In short-term adhesion assays to measure cell affinity for the different substrates, cells in the O-2A lineage bound preferentially to N-cadherin while type-1 astrocytes preferentially bound to extracellular matrix components. The cells in the O-2A lineage also developed distinctive morphologies on different substrates after incubation for 4 days. Type-2 astrocytes and oligodendrocytes produced very large membranous expansions on N-cadherin. Measurements of BrdU incorporation indicated that the substrates did not significantly influence cell proliferation rates. Our results showed that O-2A progenitor cells, oligodendrocytes, type-1 astrocytes, and type-2 astrocytes possess different complements of receptors for the adhesion molecules in their environment and that their morphological differentiation can be dramatically altered by these extracellular signals.