Autophagy collaborates with apoptosis pathways to control oligodendrocyte number

Oligodendrocytes are the sole myelin-producing cells in the central nervous system. Oligodendrocyte num-ber is tightly controlled across diverse brain regions to match local axon type and number, yet the underlying mechanisms remain unclear. Here, we show that autophagy, an evolutionarily conserved cellular process that promotes cell survival under physiological conditions, elicits premyelinating oligodendrocyte apoptosis during development. Autophagy flux is increased in premyelinating oligodendrocytes, and its genetic blockage causes ectopic oligodendrocyte survival throughout the entire brain. Autophagy functions cell autonomously in the premyelinating oligodendrocyte to trigger cell apoptosis, and it genetically interacts with the TFEB pathway to limit oligodendrocyte number across diverse brain regions. Our results provide in vivo evidence showing that autophagy promotes apoptosis in mammalian cells under physiological con-ditions and reveal key intrinsic mechanisms governing oligodendrogenesis.

Automated summary

Oligodendrocytes are the only cells responsible for producing myelin in the central nervous system. The number of oligodendrocytes is tightly regulated in different brain regions to match the type and quantity of local axons, but the underlying mechanisms are still unclear. This study shows that autophagy, a cellular process that promotes cell survival under normal conditions, leads to apoptosis of premyelinating oligodendrocytes during development. Autophagy functions autonomously in premyelinating oligodendrocytes to trigger cell apoptosis, and it interacts with the TFEB pathway to control the number of oligodendrocytes in diverse brain regions. These findings provide in vivo evidence that autophagy plays a role in promoting apoptosis in mammalian cells under physiological conditions and uncover important intrinsic mechanisms governing oligodendrogenesis.