Dysfunction of Trio GEF1 involves in excitatory/inhibitory imbalance and autism-like behaviors through regulation of interneuron migration.
作者： Weihua Yue , Weihua Yue , Dai Zhang , Dai Zhang , Jun Li
DOI: 10.1038/S41380-021-01109-X
关键词:
摘要: Autism spectrum disorders (ASDs) are a group of highly inheritable neurodevelopmental disorders. Functional mutations in TRIO, especially the GEF1 domain, strongly implicated ASDs, whereas underlying neurobiological pathogenesis and molecular mechanisms remain to be clarified. Here we characterize abnormal morphology behavior embryonic migratory interneurons (INs) upon Trio deficiency or mutation mice, which mediated by GEF1-Rac1 activation involved SDF1α/CXCR4 signaling. In addition, migration deficits specifically associated with altered neural microcircuit, decreased inhibitory neurotransmission, autism-like behaviors, reminiscent some features observed patients ASDs. Furthermore, restoring excitatory/inhibitory (E/I) imbalance via GABA signaling rescues deficits. Our findings demonstrate critical role IN E/I balance, related autism-related behavioral phenotypes.
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