Dramatic changes in morphology and myelin protein expression take place during the differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes. Fyn tyrosine kinase was reported to play a central role in the differentiation process. Molecules that could induce Fyn signaling have not been studied. Such molecules are promising therapeutic targets in demyelinating diseases. We provide evidence that the common γ chain of immunoglobulin Fc receptors (FcRγ) is expressed in OPCs and has a role in triggering Fyn signaling. FcRγ cross-linking by immunoglobulin G on OPCs promotes the activation of Fyn signaling and induces rapid morphological differentiation with upregulation of myelin basic protein (MBP) expression levels. Mice deficient in FcRγ are hypomyelinated, and a significant reduction in MBP content is evident. Our findings indicate that the FcRγ-Fyn-MBP cascade is pivotal during the differentiation of OPCs into myelinating oligodendrocytes, revealing an unexpected involvement of immunological molecules.
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