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Bcl11a deficiency in cerebellar Purkinje cells causes ataxia and autistic-like behavior by altering Vav3

Molecular Psychiatry volume 31, pages 802–818 (2026)Cite this article

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Abstract

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 identified cerebellar pathology in patients with BCL11A variants, the specific roles of this gene in cerebellar function and its relationship to clinical symptoms remain unclear. In this study, we demonstrate that Bcl11a is predominantly expressed in Purkinje cells (PCs) of both the developing and adult mouse cerebellum. Conditional deletion of Bcl11a in PCs leads to impaired PC survival, disrupts dendritic 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 and reduced excitatory synaptic inputs from both parallel and climbing fibers, while maintaining normal intrinsic excitability and inhibitory synaptic inputs. Moreover, we identify Vav3 (guanosine nucleotide exchange factor 3) as a downstream target of Bcl11a in PCs and demonstrate that Vav3 overexpression partially rescues both PC dysfunction and abnormal motor and social behaviors in Bcl11a-deficient mice. Together, these findings establish Bcl11a’s critical role in PC function and provide mechanistic insight into how BCL11A mutations contribute to cerebellar dysfunction in psychiatric disorders such as ASD.

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Fig. 1: Cerebellar pathological changes in Bcl11a-cKO mice.
Fig. 2: Bcl11a-cKO mice exhibit ataxia and social deficits.
Fig. 3: Abnormal spontaneous firing activity and excitatory synaptic transmission in Bcl11a-cKO PCs.
Fig. 4: snRNA-seq and gene expression analysis.
Fig. 5: Vav3 Overexpression rescues dendritic morphology and synaptic function of PCs in Bcl11a-cKO mice.
Fig. 6: Vav3 overexpression rescues ataxia and social deficits in Bcl11a-cKO mice.

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Data availability

The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive in National Genomics Data Center, China National Center for Bioinformation / Beijing Institute of Genomics, Chinese Academy of Sciences (GSA: CRA026084) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa. The published article includes all datasets generated or analyzed during this study.

References

  1. Kheradmand A, Zee DS. Cerebellum and ocular motor control. Front Neurol. 2011;2:53.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Thach W. A role for the cerebellum in learning movement coordination. Neurobiol Learn Mem. 1998;70:177–88.

    Article  PubMed  CAS  Google Scholar 

  3. Ioffe M. Cerebellar control of posture. Handbook of the Cerebellum and Cerebellar Disorders. Springer; 2021. p. 1379–98.

    Google Scholar 

  4. Morton SM, Bastian AJ. Cerebellar control of balance and locomotion. Neuroscientist. 2004;10:247–59.

    Article  PubMed  Google Scholar 

  5. Van Overwalle F, Manto M, Cattaneo Z, Clausi S, Ferrari C, Gabrieli JD, et al. Consensus paper: cerebellum and social cognition. Cerebellum. 2020;19:833–68.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Van Overwalle F, Manto M, Leggio M, Delgado-García JM. The sequencing process generated by the cerebellum crucially contributes to social interactions. Med Hypotheses. 2019;128:33–42.

    Article  PubMed  Google Scholar 

  7. Murdoch BE. The cerebellum and language: historical perspective and review. Cortex. 2010;46:858–68.

    Article  PubMed  Google Scholar 

  8. Mariën P, Borgatti R. Language and the cerebellum. Handb Clin Neurol. 2018;154:181–202.

    Article  PubMed  Google Scholar 

  9. Schmahmann JD. The cerebellum and cognition. Neurosci Lett. 2019;688:62–75.

    Article  PubMed  CAS  Google Scholar 

  10. Schmahmann JD, Caplan D. Cognition, emotion and the cerebellum. Brain. 2006;129:290–2.

    Article  PubMed  Google Scholar 

  11. Andreasen NC, Pierson R. The role of the cerebellum in schizophrenia. Biol Psychiatry. 2008;64:81–88.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Picard H, Amado I, Mouchet-Mages S, Olié J-P, Krebs M-O. The role of the cerebellum in schizophrenia: an update of clinical, cognitive, and functional evidences. Schizophrenia Bull. 2008;34:155–72.

    Article  Google Scholar 

  13. Becker EB, Stoodley CJ. Autism spectrum disorder and the cerebellum. Int Rev Neurobiol. 2013;113:1–34.

    Article  PubMed  CAS  Google Scholar 

  14. Hampson DR, Blatt GJ. Autism spectrum disorders and neuropathology of the cerebellum. Front Neurosci. 2015;9:420.

    Article  PubMed  PubMed Central  Google Scholar 

  15. D’Mello AM, Stoodley CJ. Cerebro-cerebellar circuits in autism spectrum disorder. Front Neurosci. 2015;9:408.

    PubMed  PubMed Central  Google Scholar 

  16. van der Heijden ME, Gill JS, Sillitoe RV. Abnormal cerebellar development in autism spectrum disorders. Dev Neurosci. 2021;43:181–90.

    Article  PubMed  Google Scholar 

  17. Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain. 1998;121:561–79.

    Article  PubMed  Google Scholar 

  18. Schmahmann JD. Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci. 2004;16:367–78.

    Article  PubMed  Google Scholar 

  19. Mosconi MW, Wang Z, Schmitt LM, Tsai P, Sweeney JA. The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders. Front Neurosci. 2015;9:156522.

    Article  Google Scholar 

  20. Whitney ER, Kemper TL, Bauman ML, Rosene DL, Blatt GJ. Cerebellar Purkinje cells are reduced in a subpopulation of autistic brains: a stereological experiment using calbindin-D28k. Cerebellum. 2008;7:406–16.

    Article  PubMed  CAS  Google Scholar 

  21. Skefos J, Cummings C, Enzer K, Holiday J, Weed K, Levy E, et al. Regional alterations in purkinje cell density in patients with autism. PLoS ONE. 2014;9:e81255.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Peter S, Ten Brinke MM, Stedehouder J, Reinelt CM, Wu B, Zhou H, et al. Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice. Nat Commun. 2016;7:12627.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Gibson JM, Vazquez AH, Yamashiro K, Jakkamsetti V, Ren C, Lei K, et al. Cerebellar contribution to autism-relevant behaviors in fragile X syndrome models. Cell Rep. 2023;42:113533.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Xu F-X, Wang X-T, Cai X-Y, Liu J-Y, Guo J-W, Yang F, et al. Purkinje-cell-specific MeCP2 deficiency leads to motor deficits and autistic-like behavior due to aberrations in PTP1B-TrkB-SK signaling. Cell Rep. 2023;42:113559.

    Article  PubMed  CAS  Google Scholar 

  25. Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, Leech JM, et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature. 2012;488:647–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Cupolillo D, Hoxha E, Faralli A, De Luca A, Rossi F, Tempia F, et al. Autistic-like traits and cerebellar dysfunction in Purkinje cell PTEN knock-out mice. Neuropsychopharmacology. 2016;41:1457–66.

    Article  PubMed  Google Scholar 

  27. Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, et al. The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. Blood. 2001;98:3413–20.

    Article  PubMed  CAS  Google Scholar 

  28. Simon R, Wiegreffe C, Britsch S. Bcl11 transcription factors regulate cortical development and function. Front Mol Neurosci. 2020;13:51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Du H, Wang Z, Guo R, Yang L, Liu G, Zhang Z, et al. Transcription factors Bcl11a and Bcl11b are required for the production and differentiation of cortical projection neurons. Cereb Cortex. 2022;32:3611–32.

    Article  PubMed  Google Scholar 

  30. Wiegreffe C, Simon R, Peschkes K, Kling C, Strehle M, Cheng J, et al. Bcl11a (Ctip1) controls migration of cortical projection neurons through regulation of Sema3c. Neuron. 2015;87:311–25.

    Article  PubMed  CAS  Google Scholar 

  31. Kuo T-Y, Hong C-J, Hsueh Y-P. Bcl11A/CTIP1 regulates expression of DCC and MAP1b in control of axon branching and dendrite outgrowth. Mol Cell Neurosci. 2009;42:195–207.

    Article  PubMed  CAS  Google Scholar 

  32. Dias C, Estruch SB, Graham SA, McRae J, Sawiak SJ, Hurst JA, et al. BCL11A haploinsufficiency causes an intellectual disability syndrome and dysregulates transcription. Am J Hum Genet. 2016;99:253–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Thompson CL, Ng L, Menon V, Martinez S, Lee C-K, Glattfelder K, et al. A high-resolution spatiotemporal atlas of gene expression of the developing mouse brain. Neuron. 2014;83:309–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Leid M, Ishmael JE, Avram D, Shepherd D, Fraulob V, Dollé P. CTIP1 and CTIP2 are differentially expressed during mouse embryogenesis. Gene Expr Patterns. 2004;4:733–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Visel A, Thaller C, Eichele G. GenePaint. org: an atlas of gene expression patterns in the mouse embryo. Nucleic Acids Res. 2004;32:D552–D556.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Peron A, Bradbury K, Viskochil DH, Dias C BCL11A-related intellectual disability. 2019.

  37. Satterstrom FK, Kosmicki JA, Wang J, Breen MS, De Rubeis S, An J-Y, et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell. 2020;180:568–584.e523.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Peron A, D’Arco F, Aldinger KA, Smith-Hicks C, Zweier C, Gradek GA, et al. BCL11A intellectual developmental disorder: defining the clinical spectrum and genotype-phenotype correlations. Eur J Hum Genet. 2025;33:312–24.

  39. McIlwain KL, Merriweather MY, Yuva-Paylor LA, Paylor R. The use of behavioral test batteries: effects of training history. Physiol Behav. 2001;73:705–17.

    Article  PubMed  CAS  Google Scholar 

  40. Crawley JN. What’s wrong with my mouse?: behavioral phenotyping of transgenic and knockout mice. John Wiley & Sons; 2007.

    Book  Google Scholar 

  41. Van Putten M, Aartsma-Rus A, Louvain-la-Neuve L. The use of hanging wire tests to monitor muscle strength and condition over time. TREAT-NMD Neuromscular Network/Wellstone Muscular Dystrophy Center, Washington, DC. 2011;2:1–11.

    Google Scholar 

  42. Liu D, Nanclares C, Simbriger K, Fang K, Lorsung E, Le N, et al. Autistic-like behavior and cerebellar dysfunction in Bmal1 mutant mice ameliorated by mTORC1 inhibition. Mol Psychiatry. 2023;28:3727–38.

    Article  PubMed  CAS  Google Scholar 

  43. Su L-D, Shen Y. Blockade of glutamate transporters facilitates cerebellar synaptic long-term depression. Neuroreport. 2009;20:502–7.

    Article  PubMed  Google Scholar 

  44. Guo X, Yuan Y, Su X, Cao Z, Chu C, Lei C, et al. Different projection neurons of basolateral amygdala participate in the retrieval of morphine withdrawal memory with diverse molecular pathways. Mol Psychiatry. 2024;29:793–808.

    Article  PubMed  CAS  Google Scholar 

  45. Yang G, Yang Y, Song Z, Chen L, Liu F, Li Y, et al. Spliceosomal GTPase Eftud2 deficiency-triggered ferroptosis leads to Purkinje cell degeneration. Neuron. 2024;112:3452–3469.e3459.

    Article  PubMed  CAS  Google Scholar 

  46. Vladoiu MC, El-Hamamy I, Donovan LK, Farooq H, Holgado BL, Sundaravadanam Y, et al. Childhood cerebellar tumours mirror conserved fetal transcriptional programs. Nature. 2019;572:67–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Kozareva V, Martin C, Osorno T, Rudolph S, Guo C, Vanderburg C, et al. A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types. Nature. 2021;598:214–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Oberdick J, Smeyne RJ, Mann JR, Zackson S, Morgan JI. A promoter that drives transgene expression in cerebellar purkinje and retinal bipolar neurons. Science. 1990;248:223–6.

    Article  PubMed  CAS  Google Scholar 

  49. Barski JJ, Dethleffsen K, Meyer M. Cre recombinase expression in cerebellar Purkinje cells. Genesis. 2000;28:93–98.

    Article  PubMed  CAS  Google Scholar 

  50. Fatemi SH, Halt AR, Realmuto G, Earle J, Kist DA, Thuras P, et al. Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol. 2002;22:171–5.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Soblet J, Dimov I, Graf von Kalckreuth C, Cano‐Chervel J, Baijot S, Pelc K, et al. BCL11A frameshift mutation associated with dyspraxia and hypotonia affecting the fine, gross, oral, and speech motor systems. Am J Med Genet Part A. 2018;176:201–8.

    Article  PubMed  CAS  Google Scholar 

  52. Liu X-X, Chen X-H, Zheng Z-W, Jiang Q, Li C, Yang L, et al. BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination. Signal Transduct Target Ther. 2022;7:170.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Vinueza Veloz M, Buijsen R, Willemsen R, Cupido A, Bosman LW, Koekkoek SK, et al. The effect of an mGluR5 inhibitor on procedural memory and avoidance discrimination impairments in Fmr1 KO mice. Genes Brain Behav. 2012;11:325–31.

    Article  PubMed  CAS  Google Scholar 

  54. Vinueza Veloz MF, Zhou K, Bosman LW, Potters J-W, Negrello M, Seepers RM, et al. Cerebellar control of gait and interlimb coordination. Brain Structure Funct. 2015;220:3513–36.

    Article  Google Scholar 

  55. Takeo YH, Shuster SA, Jiang L, Hu MC, Luginbuhl DJ, Rülicke T, et al. GluD2-and Cbln1-mediated competitive interactions shape the dendritic arbors of cerebellar Purkinje cells. Neuron. 2021;109:629–644.e628.

    Article  PubMed  CAS  Google Scholar 

  56. Silvestri L, Paciscopi M, Soda P, Biamonte F, Iannello G, Frasconi P, et al. Quantitative neuroanatomy of all Purkinje cells with light sheet microscopy and high-throughput image analysis. Front Neuroanat. 2015;9:68.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Woodruff-Pak D. Stereological estimation of Purkinje neuron number in C57BL/6 mice and its relation to associative learning. Neuroscience. 2006;141:233–43.

    Article  PubMed  CAS  Google Scholar 

  58. Bustelo XR. Vav family exchange factors: an integrated regulatory and functional view. Small GTPases. 2014;5:e973757.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Wegrzyn D, Wegrzyn C, Tedford K, Fischer K-D, Faissner A. Deletion of the nucleotide exchange factor Vav3 enhances axonal complexity and synapse formation but tampers activity of hippocampal neuronal networks in vitro. Int J Mol Sci. 2020;21:856.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Quevedo C, Sauzeau V, Menacho-Márquez M, Castro-Castro A, Bustelo XR. Vav3-deficient mice exhibit a transient delay in cerebellar development. Mol Biol Cell. 2010;21:1125–39.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Hancarova M, Simandlova M, Drabova J, Mannik K, Kurg A, Sedlacek Z. A patient with de novo 0.45 Mb deletion of 2p16. 1: the role of BCL11A, PAPOLG, REL, and FLJ16341 in the 2p15‐p16. 1 microdeletion syndrome. Am J Med Genet Part A. 2013;161:865–70.

    Article  Google Scholar 

  62. Balci TB, Sawyer SL, Davila J, Humphreys P, Dyment DA. Brain malformations in a patient with deletion 2p16. 1: A refinement of the phenotype to BCL11A. Eur J Med Genet. 2015;58:351–4.

    Article  PubMed  Google Scholar 

  63. Lévy J, Coussement A, Dupont C, Guimiot F, Baumann C, Viot G, et al. Molecular and clinical delineation of 2p15p16. 1 microdeletion syndrome. Am J Med Genet Part A. 2017;173:2081–7.

    Article  PubMed  Google Scholar 

  64. John A, Brylka H, Wiegreffe C, Simon R, Liu P, Jüttner R, et al. Bcl11a is required for neuronal morphogenesis and sensory circuit formation in dorsal spinal cord development. Development. 2012;139:1831–41.

    Article  PubMed  CAS  Google Scholar 

  65. Tolve M, Ulusoy A, Patikas N, Islam KUS, Bodea GO, Öztürk E, et al. The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons. Cell Rep. 2021;36:109697.

    Article  PubMed  CAS  Google Scholar 

  66. Greig LC, Woodworth MB, Greppi C, Macklis JD. Ctip1 controls acquisition of sensory area identity and establishment of sensory input fields in the developing neocortex. Neuron. 2016;90:261–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Wang R, Tan J, Guo J, Zheng Y, Han Q, So K-F, et al. Aberrant development and synaptic transmission of cerebellar cortex in a VPA induced mouse autism model. Front Cell Neurosci. 2018;12:500.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Main SL, Kulesza RJ. Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia. Neuroscience. 2017;340:34–47.

    Article  PubMed  CAS  Google Scholar 

  69. Ehret G, Bernecker C. Low-frequency sound communication by mouse pups (Mus musculus): wriggling calls release maternal behaviour. Anim Behav. 1986;34:821–30.

    Article  Google Scholar 

  70. Hanzel M, Fernando K, Maloney SE, Horn Z, Gong S, Mätlik K, et al. Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties. Proc Natl Acad Sci. 2024;121:e2405901121.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Korenke GC, Schulte B, Biskup S, Neidhardt J, Owczarek-Lipska M. A novel de novo frameshift mutation in the BCL11A gene in a patient with intellectual disability syndrome and epilepsy. Mol Syndromol. 2020;11:135–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Beleford DT, Van Ziffle J, Hodoglugil U, Slavotinek AM. A missense variant, p.(Ile269Asn), in MC4R as a secondary finding in a child with BCL11A-related intellectual disability. Eur J Med Genet. 2020;63:103969.

    Article  PubMed  Google Scholar 

  73. Bruce L, Peter B. Three children with different de novo BCL11A variants and diverse developmental phenotypes, but shared global motor discoordination and apraxic speech: Evidence for a functional gene network influencing the developing cerebellum and motor and auditory cortices. Am J Med Genet Part A. 2022;188:3401–15.

    Article  PubMed  Google Scholar 

  74. Matson ML, Matson JL, Beighley JS. Comorbidity of physical and motor problems in children with autism. Res Dev Disabil. 2011;32:2304–8.

    Article  PubMed  Google Scholar 

  75. Licari MK, Alvares GA, Varcin K, Evans KL, Cleary D, Reid SL, et al. Prevalence of motor difficulties in autism spectrum disorder: analysis of a population-based cohort. Autism Res. 2020;13:298–306.

    Article  PubMed  Google Scholar 

  76. Koekkoek S, Yamaguchi K, Milojkovic B, Dortland B, Ruigrok T, Maex R, et al. Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome. Neuron. 2005;47:339–52.

    Article  PubMed  CAS  Google Scholar 

  77. Hoebeek F, Stahl J, Van Alphen A, Schonewille M, Luo C, Rutteman M, et al. Increased noise level of purkinje cell activities minimizes impact of their modulation during sensorimotor control. Neuron. 2005;45:953–65.

    Article  PubMed  CAS  Google Scholar 

  78. Aldinger KA, Thomson Z, Phelps IG, Haldipur P, Deng M, Timms AE, et al. Spatial and cell type transcriptional landscape of human cerebellar development. Nat Neurosci. 2021;24:1163–75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Movilla N, Bustelo XR. Biological and regulatory properties of Vav-3, a new member of the Vav family of oncoproteins. Mol Cell Biol. 1999;19:7870–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Aoki K, Nakamura T, Fujikawa K, Matsuda M. Local phosphatidylinositol 3, 4, 5-trisphosphate accumulation recruits Vav2 and Vav3 to activate Rac1/Cdc42 and initiate neurite outgrowth in nerve growth factor-stimulated PC12 cells. Mol Biol Cell. 2005;16:2207–17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Toumaniantz G, Ferland-McCollough D, Cario-Toumaniantz C, Pacaud P, Loirand G. The Rho protein exchange factor Vav3 regulates vascular smooth muscle cell proliferation and migration. Cardiovascular Res. 2010;86:131–40.

    Article  CAS  Google Scholar 

  82. Hornstein I, Alcover A, Katzav S. Vav proteins, masters of the world of cytoskeleton organization. Cell Signal. 2004;16:1–11.

    Article  PubMed  CAS  Google Scholar 

  83. Ulc A, Gottschling C, Schäfer I, Wegrzyn D, van Leeuwen S, Luft V, et al. Involvement of the guanine nucleotide exchange factor Vav3 in central nervous system development and plasticity. Biol Chem. 2017;398:663–75.

    Article  PubMed  CAS  Google Scholar 

  84. Luft V, Reinhard J, Shibuya M, Fischer KD, Faissner A. The guanine nucleotide exchange factor Vav3 regulates differentiation of progenitor cells in the developing mouse retina. Cell Tissue Res. 2015;359:423–40.

    Article  PubMed  CAS  Google Scholar 

  85. Peter S, De Zeeuw CI, Boeckers TM, Schmeisser MJ. Cerebellar and striatal pathologies in mouse models of autism spectrum disorder. Transl Anat Cell Biol Autism Spectr Disord. 2017;224:103–19.

    Google Scholar 

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2021ZD0202500), the Natural Science Foundation of China (31930044, 31725012), the Foundation of Shanghai Municipal Education Commission (2019-01-07-00-07-E00062), the Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01), the Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01) and ZJLab to YCY.

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  1. These authors contributed equally: Jie Zhang, Yuan-Xin Li.

Authors and Affiliations

  1. Jing’an District Central Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China

    Jie Zhang, Yuan-Xin Li, Qian Huang, Yu Yuan, Jun-Yang Chen, Fu-Wei Yang, Lin Yang, Lin-Yun Liu & Yong-Chun Yu

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Contributions

YCY conceived the study. YCY and JZ wrote the manuscript. YCY, LYL, QH, and JZ designed the experiments. JZ performed the immunohistochemistry, behavioral tests, MRI acquisition, single-cell sequencing analysis, and virus injection experiments. YXL conducted the patch-clamp recordings. JZ and YXL analyzed the data. QH assisted with the behavioral data analysis. YY contributed to the electrophysiology and immunohistochemistry experiments. JYC assisted with standardized MRI acquisition. FWY provided support for the immunohistochemistry experiments. LY assisted with single-cell data analysis. All authors contributed to manuscript revision, read, and approved the submitted version.

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Correspondence to Lin-Yun Liu or Yong-Chun Yu.

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The study was approved by Ethics Committee of Fudan University (approval number: FE21173). All methods were performed in accordance with the ethical standards of Fudan University and complied with the relevant institutional and national guidelines and regulations for the care and use of laboratory animals. This study did not involve human participants, and informed consent was not required. No identifiable images from human participants are included in this article.

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Zhang, J., Li, YX., Huang, Q. et al. Bcl11a deficiency in cerebellar Purkinje cells causes ataxia and autistic-like behavior by altering Vav3. Mol Psychiatry 31, 802–818 (2026). https://doi.org/10.1038/s41380-025-03175-x

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