Elucidating the mechanism of myelination : FcRγ-Fyn-MBP stream is critical for the CNS myelination.

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Elucidation of the mechanism of CNS myelinogenesis is ultimately required to cure demyelinating disease. We have elucidated the mechanism whereby the γ chain of immunoglobulin Fc recepter(FcR γ ), an essential signaling molecule of the immune system, functions as a trigger for oligodendroglial myelinogenesis. FcR γ signaling results in the up-regulation of Fyn tyrosine kinase (Fyn) and myelin basic protein (MBP) expression levels, in addition to the morphological differentiation of oligodendroglia. Mice deficient in FcR γ demonstrate severely disturbed myelinogenesis, similar to the defect observed in mice deficient in either Fyn or MBP. FcR γ -Fyn double deficient mice exhibit severer hypomyelination and decrease in MBP than those of both single mutant mice, implying that FcR γ -Fyn-MBP cascade is indeed critical for the myelinogenesis. We have also detected expression of Fc recepters specific for immunoglobulin G in conjunction with FcR γ in oligodendroglia, suggesting immunogloblins may contribute to myelinogenesis. Expression of CD45, a regulator of Fyn, in oligodendroglia suggests the involvement of this molecule in the proposed mechanism. Our findings uncover a new connection between the brain and the immune system involved in myelinogenesis, introducing a novel therapeutic avenue leading to a possible cure for demyelinating disease.