A new extracellular matrix inhibitor of oligodendrocyte maturation: Fibulin-2

Impairment of oligodendrocytes and myelin contributes to neurological disorders including multiple sclerosis (MS). A contributor to inefficient remyelination is the altered extracellular matrix (ECM) in lesions that remains to be better defined. We have identified fibulin-2 (FBLN2) as a highly upregulated ECM component in lesions of MS. The inhibitory role of FBLN2 was suggested in the experimental autoimmune encephalomyelitis (EAE) model in which genetic FBLN2 deficiency alleviated disease severity. To investigate the mechanisms of FBLN2, mouse OPCs were plated in control or FBLN2 coated wells in differentiation media for 6h. Bulk RNA sequencing was performed to identify up- or down-regulated genes. Collectively, our findings suggest that FBLN2 impairs oligodendrogenesis through engaging the Notch signaling pathway.