Ddx20, DEAD-box helicase 20 is essential for maintaining microglial homeostasis.

The properties of central nervous system microglia adjust dynamically in response to various environmental signals, under both normal and disease conditions. However, the regulation of microglia homeostasis is not well understood. We hypothesize that the DEAD-box RNA helicase Ddx20 plays a key role in maintaining microglial homeostasis. To test this hypothesis, we generated mice with conditional deletion of Ddx20 in microglia using Iba1-iCre knock-in mice, and analyzed the effects of spinal cord injury and aging. Ddx20 ablation led to a drastic alteration of microglial morphology and a marked downregulation of gene networks involved in maintaining microglial identity, immune surveillance, and homeostatic functions; these effects become more prominent with spinal cord injury and aging. Our findings provide novel insights into the role of Ddx20 as a molecular regulator of microglial homeostasis and response to central nervous system injury.