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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, STING^cKO mice display autistic-like behaviors. In NPCs, STING specifically recruits IKK? and activates nuclear factor ?B (NF-?B) through phosphorylation. NF-?B binds to ALX4 promoter and triggers ALX4 transcription. In addition, tumor necrosis factor ?, an activator of NF-?B, 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.

SUBMITTER: Zhang D

PROVIDER: S-EPMC7710002 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Zhang Dongming D Liu Chang C Li Hong H Jiao Jianwei J

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20201103 23

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, STING<sup>cKO</sup> mice display autistic-like behaviors. In NPCs, STING specifically recruits IKK ...[more]

PMID: 33304758

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