摘要：SummaryDuplication and haploinsufficiency of the USP7 gene are implicated in autism spectrum disorders (ASD), but the role for USP7 in neurodevelopment and contribution to ASD pathogenesis remain unknown. We find that in primary neurons, overexpression of USP7 increases dendritic branch number and total dendritic length, whereas knockdown leads to opposite alterations. Besides, USP7 deubiquitinates the X-linked inhibitor of apoptosis protein (XIAP). The USP7-induced increase in XIAP suppresses caspase 3 activity, leading to a reduction in tubulin cleavage and suppression of dendritic pruning. When USP7 is introduced into the brains of prenatal mice viain utero electroporation(IUE), it results in abnormal migration of newborn neurons and increased dendritic arborization. Importantly, intraventricular brain injection of AAV-USP7 in P0 mice leads to autistic-like phenotypes including aberrant social interactions, repetitive behaviors, as well as changes in somatosensory sensitivity. These findings provide new insights in USP7-related neurobiological functions and its implication in ASD.Graphical abstractDisplay OmittedHighlights•Overexpression of USP7 increases dendritic arborization•USP7 targets XIAP for deubiquitination and regulates XIAP proteostasis in neurons•USP7 regulates dendritic remodeling via the XIAP-caspase 3-tubulin pathway•Prenatal overexpression of USP7 in mice leads to autistic-like behaviorsBehavioral neuroscience; Biological sciences; Cellular neuroscience; Neuroscience
