Deficiency of STING Signaling in Embryonic Cerebral Cortex Leads to Neurogenic Abnormalities and Autistic-Like Behaviors

Abstract

STING is known as a central adaptor for sensing cytosolic DNA sensing. Recent studies have provided evidence that STING response is divergent among different cell types. Here, this work demonstrates that STING controls neural progenitor cells (NPCs) by sensing DNA damage in NPCs. The deletion of STING reduces neuronal differentiation and increases proliferation of mouse and human NPCs. Furthermore, STINGcKO mice display autistic-like behaviors. In NPCs, STING specifically recruits IKKβ and activates nuclear factor κB (NF-κB) through phosphorylation. NF-κB binds to ALX4 promoter and triggers ALX4 transcription. In addition, tumor necrosis factor α, an activator of NF-κB, can rescue some phenotypes caused by STING deletion in mice. Together, the findings show that STING signaling is essential for neuronal gene expression program and has profound consequences on brain function.