The present invention is based on the discovery that oligodendrocyte-myelin glycoprotein (OMgp), which is ex-pressed by oligodendrocytes and CNS myelin, negatively regulates oligodendrocyte and neuronal differentiation and survival. Based on these discoveries, the invention relates generally to methods of promoting neuronal and oligodendrocyte survival and differentiation by administration of an OMgp anatagonist. Additionally, the invention generally relates to methods of treating various diseases, disorders or injuries associated with demyelination, dysmyelination, oligodendrocyte/neuronal cell death, axonal injury and/or differentiation by the administration of an OMgp antagonist.