Ligands and receptors in ErbB signaling pathways have been genetically linked to schizophrenia or other psychiatric disorders.Despite the strong evidence from genetically engineered mice for the necessity of ErbB signaling in peripheral myelination,controversial results in central myelination refrained our understanding on its contribution to pathophysiology of schizophrenics with white matter lesion.We adopted inducible strategies to manipulate ErbB signaling in oligodendroglial progenitors and/or differentiated oligodendrocytes during adolescence,and revealed contribution of the disease-associated signaling to the pathogenesis in central myelin.Similar to the peripheral nervous system,ErbB signaling was not required for maintenance of myelin formed by mature oligodendrocytes.However,excessive ErbB activation,which is frequently detected in schizophrenic brain,in mature oligodendrocytes caused myelin over expanding to collapse,while that in oligodendroglial progenitor cells inhibited cell proliferation so that axons were hypo-myelinated.On the other hand,suppressed ErbB activation in oligodendroglial progenitor cells resulted in increased proliferation but inhibited myelinating ability of newly differentiated oligodendrocytes.Differential regulation by ErbB signaling on oligodendroglial lineage cells at different stages during adolescence emphasizes a careful and precise therapeutic intervention for related diseases.