FGF signaling induces disease-associated oligodendrocyte states and drives myelin pathology

Activating FGF signaling in mature oligodendrocytes induces disease-associated oligodendrocyte programs and triggers myelin disruption in vivo, linking the FGF/FGFR axis to pathology.

• Why it matters: Disease-associated oligodendrocytes (DAOs) are seen in multiple sclerosis and other CNS disorders, but the signals that generate them and their role in myelin damage are unclear.
• What they did: Screening disease-linked secreted factors in purified oligodendrocyte cultures identified FGF1 and FGF2 as potent inducers of a DAO-like transcriptional state with myelin-membrane shedding; mouse experiments then activated or inhibited oligodendrocyte FGF signaling.
• The result: Oligodendrocyte FGF activation elicited DAO programs and myelin disruption, while FGF inhibition suppressed DAO induction in a mouse model of multiple sclerosis; post-mortem multiple sclerosis tissue showed a concordant DAO-like state with increased FGF/FGFR axis engagement.

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