The bone transcription factor Osterix controls extracellular matrix and node of Ranvier related gene expression in oligodendrocytes [RNA-seq]

Oligodendrocytes are the primary producers of many extracellular matrix (ECM) related proteins found in the central nervous system (CNS), thereby, these cells play a critical role in the determination of brain stiffness, node of Ranvier formation, perinodal ECM deposition and perineuronal net formation. The transcription factors that control ECM related gene expression in oligodendrocytes remain unknown. Here, we found that the transcription factor Osterix (also known as Sp7) binds in proximity to genes important for CNS ECM and node of Ranvier formation and mediates their expression. Oligodendrocyte specific ablation of Sp7 changes ECM composition and brain stiffness, and results in aberrant node of Ranvier formation. Sp7 is known to control osteoblast maturation and bone formation. Our comparative analyses suggests that Sp7 plays a conserved biological role in oligodendrocytes and in bone forming cells, where it mediates brain and bone tissue stiffness by controlling the expression of ECM components. To explore the role of Sp7 ablation on gene expression, total RNA-seq data from primary cultured oligodendrocytes derived from the brains of WT and Sp7-ablated mice was compared.