c‑Jun N‑terminal kinase 1 (JNK1) modulates oligodendrocyte progenitor cell architecture, proliferation and myelination.

During Central Nervous System (CNS) development, myelinating oligodendrocytes (OLs) arise from highly ramified and proliferative precursors called oligodendrocyte progenitor cells (OPCs). OPC architecture, proliferation and maturation in myelinating cells are finely regulated by the interplay of cell-intrinsic and environmental factors. A variety of extrinsic cues converge on the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK) pathway. However, the exact role of the members of the ERK/MAPK family in the regulation of OL/OPC biology remains to be investigated. Following the germinal ablation (KO) of the MAPK c-Jun N-Terminal Kinase isoform 1 (JNK1), a significant reduction of myelin in the cerebral cortex and corpus callosum is found at both postnatal and adult stages. Such hypomyelination is accompanied by higher OPC density and proliferation during the first weeks of life, consistent with a transient alteration of mechanisms regulating OPC self-renewal and differentiation. JNK1 KO OPCs also show smaller occupancy territories and a less complex branching architecture in vivo. Notably, these latter phenotypes are recapitulated in pure cultures of JNK1 KO OPCs and of WT OPCs treated with the JNK inhibitor D-JNKI-1. Moreover, JNK1 KO and WT D-JNKI-1 treated OLs, while not showing alterations of their maturation potential in vitro, display a reduced surface compared to controls. These results show that JNK1 ablation cell-autonomously determines alterations of OPC proliferation and branching architecture and suggest that JNK1 signalling participates in myelination in vivo.