Bcl11a Deficiency In Cerebellar Purkinje Cells Causes Ataxia And Autisticlike Behavior By Altering Vav3 Jie Zhang Yuanxin Li Qian Huang Yu Yuan Junyang Chen Fuwei Yang Lin Yang Linyun Liu Yongchun Yu by Jie Zhang & Yuan-xin Li & Qian Huang & Yu Yuan & Jun-yang Chen & Fu-wei Yang & Lin Yang & Lin-yun Liu & Yong-chun Yu instant download after payment.

BCL11A encodes a transcription factor essential for brain development, with pathogenic variants causing intellectual disability,autism spectrum disorder (ASD), microcephaly, hypotonia, and behavioral abnormalities. While clinical studies have identifiedcerebellar pathology in patients with BCL11A variants, the specific roles of this gene in cerebellar function and its relationship toclinical symptoms remain unclear. In this study, we demonstrate that Bcl11a is predominantly expressed in Purkinje cells (PCs) ofboth the developing and adult mouse cerebellum. Conditional deletion of Bcl11a in PCs leads to impaired PC survival, disruptsdendritic morphology, reduces spine density, and results in ataxia, motor learning deficits, and autistic-like behaviors.Electrophysiological analyses reveal that Bcl11a-deficient PCs exhibit decreased frequency and regularity of spontaneous firing and1234567890();,:reduced excitatory synaptic inputs from both parallel and climbing fibers, while maintaining normal intrinsic excitability andinhibitory synaptic inputs. Moreover, we identify Vav3 (guanosine nucleotide exchange factor 3) as a downstream target of Bcl11ain PCs and demonstrate that Vav3 overexpression partially rescues both PC dysfunction and abnormal motor and social behaviorsin Bcl11a-deficient mice. Together, these findings establish Bcl11a’s critical role in PC function and provide mechanistic insight intohow BCL11A mutations contribute to cerebellar dysfunction in psychiatric disorders such as ASD.Molecular Psychiatry;