{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:33:37Z","timestamp":1792139617747,"version":"4.4.0"},"reference-count":121,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Autism spectrum disorders (ASDs) are complex neurodevelopmental conditions characterized by deficits in social interaction and communication, as well as repetitive behaviors. Although the etiology of ASD is multifactorial, with both genetic and environmental factors contributing to its development, a strong genetic basis is widely recognized. Recent research has identified numerous genetic mutations and genomic rearrangements associated with ASD-characterizing genes involved in brain development. Alterations in developmental programs are particularly harmful during critical periods of brain development. Notably, studies have indicated that genetic disruptions occurring during the second trimester of pregnancy affect cortical development, while disturbances in the perinatal and early postnatal period affect cerebellar development. The developmental defects must be viewed in the context of the role of the cerebellum in cognitive processes, which is now well established. The present review emphasizes the genetic complexity and neuropathological mechanisms underlying ASD and aims to provide insights into the cerebellar involvement in the disorder, focusing on recent advances in the molecular landscape governing its development in humans. Furthermore, we highlight when and in which cerebellar neurons the ASD-associated genes may play a role in the development of cortico\u2013cerebellar circuits. Finally, we discuss improvements in protocols for generating cerebellar organoids to recapitulate the long period of development and maturation of this organ. These models, if generated from patient-induced pluripotent stem cells (iPSC), could provide a valuable approach to elucidate the contribution of defective genes to ASD pathology and inform diagnostic and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cells13141176","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T13:34:38Z","timestamp":1720618478000},"page":"1176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Unravelling the Cerebellar Involvement in Autism Spectrum Disorders: Insights into Genetic Mechanisms and Developmental Pathways"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4531-3361","authenticated-orcid":false,"given":"Marika","family":"Guerra","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Hearth, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-8308","authenticated-orcid":false,"given":"Vanessa","family":"Medici","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Hearth, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1907-5948","authenticated-orcid":false,"given":"Gina","family":"La Sala","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, Italian National Research Council (CNR), 00015 Monterotondo Scalo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1991-3956","authenticated-orcid":false,"given":"Donatella","family":"Farini","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1097\/NMD.0b013e3182a2168a","article-title":"Diagnostic and statistical manual of mental disorders, 5th edition, and clinical utility","volume":"201","author":"First","year":"2013","journal-title":"J. Nerv. Ment. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1001\/jama.2017.12141","article-title":"The Heritability of Autism Spectrum Disorder","volume":"318","author":"Sandin","year":"2017","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1001\/jama.2013.2270","article-title":"Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism","volume":"309","author":"Christensen","year":"2013","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s10519-019-09987-2","article-title":"On the Nature of Monozygotic Twin Concordance and Discordance for Autistic Trait Severity: A Quantitative Analysis","volume":"50","author":"Castelbaum","year":"2020","journal-title":"Behav. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s10803-009-0736-1","article-title":"Relationship between Symptom Domains in Autism Spectrum Disorders: A Population Based Twin Study","volume":"39","author":"Dworzynski","year":"2009","journal-title":"J. Autism Dev. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.cell.2013.10.020","article-title":"Coexpression Networks Implicate Human Midfetal Deep Cortical Projection Neurons in the Pathogenesis of Autism","volume":"155","author":"Willsey","year":"2013","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.neuron.2014.07.016","article-title":"The cerebellum, sensitive periods, and autism","volume":"83","author":"Wang","year":"2014","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.siny.2016.04.010","article-title":"Structure-function relationships in the developing cerebellum: Evidence from early-life cerebellar injury and neurodevelopmental disorders","volume":"21","author":"Stoodley","year":"2016","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100919","DOI":"10.1016\/j.gim.2023.100919","article-title":"Contemplating syndromic autism","volume":"25","author":"Vorstman","year":"2023","journal-title":"Genet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pediatrneurol.2020.06.011","article-title":"Syndromic Autism Revisited: Review of the Literature and Lessons Learned","volume":"114","author":"Ziats","year":"2021","journal-title":"Pediatr. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1038\/nn.4420","article-title":"Lessons learned from studying syndromic autism spectrum disorders","volume":"19","author":"Sztainberg","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vyas, Y., Cheyne, J.E., Lee, K., Jung, Y., Cheung, P.Y., and Montgomery, J.M. (2021). Shankopathies in the Developing Brain in Autism Spectrum Disorders. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.775431"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000334260","article-title":"The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome)","volume":"2","author":"Phelan","year":"2012","journal-title":"Mol. Syndromol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e06085","DOI":"10.7554\/eLife.06085","article-title":"Cerebellar associative sensory learning defects in five mouse autism models","volume":"4","author":"Kloth","year":"2015","journal-title":"eLife"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s13023-022-02278-w","article-title":"A brief history of MECP2 duplication syndrome: 20-years of clinical understanding","volume":"17","author":"Ta","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Good, K.V., Vincent, J.B., and Ausi\u00f3, J. (2021). MeCP2: The Genetic Driver of Rett Syndrome Epigenetics. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.620859"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00109-002-0396-5","article-title":"Elevated methyl-CpG-binding protein 2 expression is acquired during postnatal human brain development and is correlated with alternative polyadenylation","volume":"81","author":"Balmer","year":"2003","journal-title":"J. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.jmb.2019.10.004","article-title":"The Molecular Basis of MeCP2 Function in the Brain","volume":"432","author":"Tillotson","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/85906","article-title":"Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice","volume":"27","author":"Chen","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_20","first-page":"217","article-title":"Autistic disturbances of affective contact","volume":"2","author":"Kanner","year":"1943","journal-title":"Nerv. Child"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nature13772","article-title":"Synaptic, transcriptional and chromatin genes disrupted in autism","volume":"515","author":"He","year":"2014","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/ng.3303","article-title":"Excess of rare, inherited truncating mutations in autism","volume":"47","author":"Krumm","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/ng.3039","article-title":"Most genetic risk for autism resides with common variation","volume":"46","author":"Gaugler","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.nbd.2008.08.011","article-title":"The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13","volume":"38","author":"Hogart","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1111\/febs.15258","article-title":"Angelman syndrome: A journey through the brain","volume":"287","author":"Maranga","year":"2020","journal-title":"FEBS J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1523\/JNEUROSCI.4276-14.2015","article-title":"Imbalanced Mechanistic Target of Rapamycin C1 and C2 Activity in the Cerebellum of Angelman Syndrome Mice Impairs Motor Function","volume":"35","author":"Sun","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"163ra157","DOI":"10.1126\/scitranslmed.3004655","article-title":"Decreased tonic inhibition in cerebellar granule cells causes motor dysfunction in a mouse model of Angelman syndrome","volume":"4","author":"Egawa","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.pnpbp.2019.02.012","article-title":"Copy number variants in autism spectrum disorders","volume":"92","author":"Vicari","year":"2019","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/s41588-019-0344-8","article-title":"Identification of common genetic risk variants for autism spectrum disorder","volume":"51","author":"Grove","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41398-020-00953-9","article-title":"Common genetic risk variants identified in the SPARK cohort support DDHD2 as a candidate risk gene for autism","volume":"10","author":"Matoba","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nature08451","article-title":"Genomic views of distant-acting enhancers","volume":"461","author":"Visel","year":"2009","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e74207","DOI":"10.7554\/eLife.74207","article-title":"Temporal analysis of enhancers during mouse cerebellar development reveals dynamic and novel regulatory functions","volume":"11","author":"Ramirez","year":"2022","journal-title":"eLife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9057","DOI":"10.1523\/JNEUROSCI.4385-15.2016","article-title":"A Novel and Multivalent Role of Pax6 in Cerebellar Development","volume":"36","author":"Yeung","year":"2016","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature13908","article-title":"The contribution of de novo coding mutations to autism spectrum disorder","volume":"515","author":"Iossifov","year":"2014","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.cell.2019.07.015","article-title":"Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks","volume":"178","author":"Ruzzo","year":"2019","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"He, X., Sanders, S.J., Liu, L., De Rubeis, S., Lim, E.T., Sutcliffe, J.S., Schellenberg, G.D., Gibbs, R.A., Daly, M.J., and Buxbaum, J.D. (2013). Integrated model of de novo and inherited genetic variants yields greater power to identify risk genes. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003671"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.neuron.2015.09.016","article-title":"Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci","volume":"87","author":"Sanders","year":"2015","journal-title":"Neuron"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/j.neuron.2012.12.008","article-title":"The autism sequencing consortium: Large-scale, high-throughput sequencing in autism spectrum disorders","volume":"76","author":"Buxbaum","year":"2012","journal-title":"Neuron"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.cell.2019.12.036","article-title":"Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism","volume":"180","author":"Satterstrom","year":"2020","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s41588-022-01148-2","article-title":"Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes","volume":"54","author":"Zhou","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1038\/s41588-022-01104-0","article-title":"Rare coding variation provides insight into the genetic architecture and phenotypic context of autism","volume":"54","author":"Fu","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.1016\/j.cell.2022.10.009","article-title":"Genomic architecture of autism from comprehensive whole-genome sequence annotation","volume":"185","author":"Trost","year":"2022","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nature20612","article-title":"Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism","volume":"540","author":"Parikshak","year":"2016","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"17065","DOI":"10.1038\/nrdp.2017.65","article-title":"Fragile X syndrome","volume":"3","author":"Hagerman","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Milla, L.A., Corral, L., Rivera, J., Zu\u00f1iga, N., Pino, G., Nunez-Parra, A., and Cea-Del Rio, C.A. (2023). Neurodevelopment and early pharmacological interventions in Fragile X Syndrome. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1213410"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41583-021-00432-0","article-title":"The molecular biology of FMRP: New insights into fragile X syndrome","volume":"22","author":"Richter","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/jdn.10217","article-title":"Cerebellum neuropathology and motor skill deficits in fragile X syndrome","volume":"82","author":"Chen","year":"2022","journal-title":"Int. J. Dev. Neurosci. Off. J. Int. Soc. Dev. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.neuron.2005.07.005","article-title":"Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome","volume":"47","author":"Koekkoek","year":"2005","journal-title":"Neuron"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"113533","DOI":"10.1016\/j.celrep.2023.113533","article-title":"Cerebellar contribution to autism-relevant behaviors in fragile X syndrome models","volume":"42","author":"Gibson","year":"2023","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1038\/s41591-023-02408-2","article-title":"Phenotypic effects of genetic variants associated with autism","volume":"29","author":"Rolland","year":"2023","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5748","DOI":"10.1038\/ncomms6748","article-title":"Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism","volume":"5","author":"Gupta","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature10110","article-title":"Transcriptomic analysis of autistic brain reveals convergent molecular pathology","volume":"474","author":"Voineagu","year":"2011","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.bbi.2015.02.001","article-title":"Immune mediated conditions in autism spectrum disorders","volume":"46","author":"Zerbo","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"100698","DOI":"10.1016\/j.bbih.2023.100698","article-title":"Genetic relationship between the immune system and autism","volume":"34","author":"Arenella","year":"2023","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13229-020-00334-5","article-title":"Emerging proteomic approaches to identify the underlying pathophysiology of neurodevelopmental and neurodegenerative disorders","volume":"11","author":"Murtaza","year":"2020","journal-title":"Mol. Autism"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/2040-2392-5-41","article-title":"Proteomic analysis of post mortem brain tissue from autism patients: Evidence for opposite changes in prefrontal cortex and cerebellum in synaptic connectivity-related proteins","volume":"5","author":"Broek","year":"2014","journal-title":"Mol. Autism"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"13118","DOI":"10.1038\/s41598-019-49533-y","article-title":"Proteomic Investigations of Autism Brain Identify Known and Novel Pathogenetic Processes","volume":"9","author":"Abraham","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"100250","DOI":"10.1016\/j.xgen.2022.100250","article-title":"Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders","volume":"3","author":"Pintacuda","year":"2023","journal-title":"Cell Genom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nrn1953","article-title":"The primate cortico-cerebellar system: Anatomy and function","volume":"7","author":"Ramnani","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s12311-020-01155-1","article-title":"Consensus Paper: Cerebellum and Social Cognition","volume":"19","author":"Manto","year":"2020","journal-title":"Cerebellum"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.cortex.2009.11.008","article-title":"Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing","volume":"46","author":"Stoodley","year":"2010","journal-title":"Cortex"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev-neuro-100120-092143","article-title":"Adaptive Prediction for Social Contexts: The Cerebellar Contribution to Typical and Atypical Social Behaviors","volume":"44","author":"Stoodley","year":"2021","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Mapelli, L., Soda, T., D\u2019Angelo, E., and Prestori, F. (2022). The Cerebellar Involvement in Autism Spectrum Disorders: From the Social Brain to Mouse Models. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073894"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neubiorev.2021.07.014","article-title":"The neuropathology of autism: A systematic review of post-mortem studies of autism and related disorders","volume":"129","author":"Fetit","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41593-020-00754-9","article-title":"Diversity and dynamism in the cerebellum","volume":"24","author":"Lisberger","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev-neuro-091421-125115","article-title":"The Cerebellar Cortex","volume":"45","author":"Hull","year":"2022","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Haldipur, P., Bharti, U., Alberti, C., Sarkar, C., Gulati, G., Iyengar, S., Gressens, P., and Mani, S. (2011). Preterm delivery disrupts the developmental program of the cerebellum. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023449"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1038\/s41593-021-00872-y","article-title":"Spatial and cell type transcriptional landscape of human cerebellar development","volume":"24","author":"Aldinger","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7613","DOI":"10.1038\/s41467-023-43568-6","article-title":"Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development","volume":"14","author":"Zhong","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1146\/annurev-neuro-111020-091953","article-title":"Human Cerebellar Development and Transcriptomics: Implications for Neurodevelopmental Disorders","volume":"45","author":"Haldipur","year":"2022","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1126\/science.aax7526","article-title":"Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum","volume":"366","author":"Haldipur","year":"2019","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1001\/archneur.1987.00520150073028","article-title":"Abnormal neuroanatomy in a nonretarded person with autism. Unusual findings with magnetic resonance imaging","volume":"44","author":"Courchesne","year":"1987","journal-title":"Arch. Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1002\/aur.97","article-title":"A comprehensive volumetric analysis of the cerebellum in children and adolescents with autism spectrum disorder","volume":"2","author":"Scott","year":"2009","journal-title":"Autism Res. Off. J. Int. Soc. Autism Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.pscychresns.2008.06.001","article-title":"Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder","volume":"172","author":"Webb","year":"2009","journal-title":"Psychiatry Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s12967-023-04090-x","article-title":"Altered cerebellar lobular volumes correlate with clinical deficits in siblings and children with ASD: Evidence from toddlers","volume":"21","author":"Kumar","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.nicl.2015.02.007","article-title":"Cerebellar gray matter and lobular volumes correlate with core autism symptoms","volume":"7","author":"Crocetti","year":"2015","journal-title":"NeuroImage Clin."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.biopsych.2022.05.020","article-title":"Cerebellar Atypicalities in Autism?","volume":"92","author":"Laidi","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1542\/peds.2007-1041","article-title":"Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors?","volume":"120","author":"Limperopoulos","year":"2007","journal-title":"Pediatrics"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1203\/PDR.0b013e3181e1d032","article-title":"Cerebellar injury in the premature infant is associated with impaired growth of specific cerebral regions","volume":"68","author":"Limperopoulos","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1023\/A:1019861721160","article-title":"Purkinje cell size is reduced in cerebellum of patients with autism","volume":"22","author":"Fatemi","year":"2002","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Skefos, J., Cummings, C., Enzer, K., Holiday, J., Weed, K., Levy, E., Yuce, T., Kemper, T., and Bauman, M. (2014). Regional alterations in purkinje cell density in patients with autism. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0081255"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s12311-008-0075-3","article-title":"Expression of GABA(B) receptors is altered in brains of subjects with autism","volume":"8","author":"Fatemi","year":"2009","journal-title":"Cerebellum"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.expneurol.2017.04.017","article-title":"The valproic acid-induced rodent model of autism","volume":"299","author":"Nicolini","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41398-023-02391-9","article-title":"Fetal exposure to valproic acid dysregulates the expression of autism-linked genes in the developing cerebellum","volume":"13","author":"Guerra","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1097\/WNR.0000000000001164","article-title":"Regional and sex-dependent alterations in Purkinje cell density in the valproate mouse model of autism","volume":"30","author":"Roux","year":"2019","journal-title":"Neuroreport"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.neubiorev.2016.12.037","article-title":"The BTBR mouse model of idiopathic autism\u2014Current view on mechanisms","volume":"76","author":"Meyza","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"624","DOI":"10.3390\/neurosci3040045","article-title":"Deficits in cerebellum-dependent learning and cerebellar morphology in male and female BTBR autism model mice","volume":"3","author":"Kiffmeyer","year":"2022","journal-title":"NeuroSci"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Xiao, R., Zhong, H., Li, X., Ma, Y., Zhang, R., Wang, L., Zang, Z., and Fan, X. (2020). Abnormal Cerebellar Development Is Involved in Dystonia-Like Behaviors and Motor Dysfunction of Autistic BTBR Mice. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00231"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/2040-2392-2-2","article-title":"Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome","volume":"2","author":"Greco","year":"2011","journal-title":"Mol. Autism"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.tins.2006.02.001","article-title":"The fragile X-cerebellum connection","volume":"29","author":"Huber","year":"2006","journal-title":"Trends Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.neurad.2009.12.006","article-title":"Cerebellar abnormality in children and young adults with tuberous sclerosis complex: MR and diffusion weighted imaging findings","volume":"37","author":"Ertan","year":"2010","journal-title":"J. Neuroradiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nature11310","article-title":"Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice","volume":"488","author":"Tsai","year":"2012","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"D\u2019Mello, A.M., and Stoodley, C.J. (2015). Cerebro-cerebellar circuits in autism spectrum disorder. Front. Neurosci., 9.","DOI":"10.3389\/fnins.2015.00408"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1093\/brain\/awp088","article-title":"Decreased connectivity and cerebellar activity in autism during motor task performance","volume":"132","author":"Mostofsky","year":"2009","journal-title":"Brain J. Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"8990","DOI":"10.1093\/cercor\/bhad177","article-title":"Functional connectivity of cortical-cerebellar networks in relation to sensorimotor behavior and clinical features in autism spectrum disorder","volume":"33","author":"Unruh","year":"2023","journal-title":"Cereb. Cortex"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/jcpp.12687","article-title":"Annual Research Review: Understudied populations within the autism spectrum\u2014Current trends and future directions in neuroimaging research","volume":"58","author":"Jack","year":"2017","journal-title":"J. Child Psychol. Psychiatry Allied Discip."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13229-015-0052-x","article-title":"Aberrant functioning of the theory-of-mind network in children and adolescents with autism","volume":"6","author":"Kana","year":"2015","journal-title":"Mol. Autism"},{"key":"ref_98","first-page":"260","article-title":"Altered Connectivity Between Cerebellum, Visual, and Sensory-Motor Networks in Autism Spectrum Disorder: Results from the EU-AIMS Longitudinal European Autism Project","volume":"4","author":"Oldehinkel","year":"2019","journal-title":"Biol. Psychiatry Cogn. Neurosci. Neuroimaging"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1001\/jamapsychiatry.2015.0101","article-title":"Increased Functional Connectivity Between Subcortical and Cortical Resting-State Networks in Autism Spectrum Disorder","volume":"72","author":"Cerliani","year":"2015","journal-title":"JAMA Psychiatry"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.biopsych.2015.03.024","article-title":"Cerebro-cerebellar Resting-State Functional Connectivity in Children and Adolescents with Autism Spectrum Disorder","volume":"78","author":"Khan","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.nicl.2014.01.008","article-title":"Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum","volume":"4","author":"Verly","year":"2014","journal-title":"NeuroImage Clin."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1111\/jcpp.13555","article-title":"Atypical cerebellar functional connectivity at 9 months of age predicts delayed socio-communicative profiles in infants at high and low risk for autism","volume":"63","author":"Okada","year":"2022","journal-title":"J. Child Psychol. Psychiatry Allied Discip."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.neuron.2018.10.010","article-title":"Spatial and Temporal Organization of the Individual Human Cerebellum","volume":"100","author":"Marek","year":"2018","journal-title":"Neuron"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s41598-018-37284-1","article-title":"A gene expression signature in developing Purkinje cells predicts autism and intellectual disability co-morbidity status","volume":"9","author":"Clifford","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/s41586-023-06884-x","article-title":"Cellular development and evolution of the mammalian cerebellum","volume":"625","author":"Sepp","year":"2024","journal-title":"Nature"},{"key":"ref_106","first-page":"e220008","article-title":"Structure, Function, and Genetics of the Cerebellum in Autism","volume":"7","author":"Sydnor","year":"2022","journal-title":"J. Psychiatry Brain Sci."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Brandenburg, C., Griswold, A.J., Van Booven, D.J., Kilander, M.B.C., Frei, J.A., Nestor, M.W., Dykxhoorn, D.M., Pericak-Vance, M.A., and Blatt, G.J. (2022). Transcriptomic analysis of isolated and pooled human postmortem cerebellar Purkinje cells in autism spectrum disorders. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.944837"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"eade1283","DOI":"10.1126\/scitranslmed.ade1283","article-title":"A single-cell genomic atlas for maturation of the human cerebellum during early childhood","volume":"15","author":"Ament","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/978-1-4939-9554-7_29","article-title":"The Contribution of Inflammation to Autism Spectrum Disorders: Recent Clinical Evidence","volume":"2011","author":"Prata","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"12129","DOI":"10.1523\/JNEUROSCI.1849-16.2016","article-title":"Cerebellar Shank2 Regulates Excitatory Synapse Density, Motor Coordination, and Specific Repetitive and Anxiety-Like Behaviors","volume":"36","author":"Ha","year":"2016","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"12627","DOI":"10.1038\/ncomms12627","article-title":"Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice","volume":"7","author":"Peter","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s12311-017-0913-2","article-title":"A Simplified Method for Generating Purkinje Cells from Human-Induced Pluripotent Stem Cells","volume":"17","author":"Watson","year":"2018","journal-title":"Cerebellum"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e67074","DOI":"10.7554\/eLife.67074","article-title":"Altered temporal sequence of transcriptional regulators in the generation of human cerebellar granule cells","volume":"10","author":"Behesti","year":"2021","journal-title":"eLife"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1038\/s41380-018-0018-4","article-title":"Purkinje cells derived from TSC patients display hypoexcitability and synaptic deficits associated with reduced FMRP levels and reversed by rapamycin","volume":"23","author":"Sundberg","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.celrep.2014.12.051","article-title":"Self-Organization of Polarized Cerebellar Tissue in 3D Culture of Human Pluripotent Stem Cells","volume":"10","author":"Muguruma","year":"2015","journal-title":"Cell Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"12959","DOI":"10.1038\/s41598-021-91846-4","article-title":"High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids","volume":"11","author":"Nayler","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.stem.2023.11.013","article-title":"Human cerebellar organoids with functional Purkinje cells","volume":"31","author":"Atamian","year":"2024","journal-title":"Cell Stem Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.biopsych.2022.11.017","article-title":"What Have Organoids and Assembloids Taught Us About the Pathophysiology of Neuropsychiatric Disorders?","volume":"93","author":"Levy","year":"2023","journal-title":"Biol. Psychiatry"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41576-020-0231-2","article-title":"A framework for an evidence-based gene list relevant to autism spectrum disorder","volume":"21","author":"Schaaf","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41398-019-0390-0","article-title":"Neurodevelopmental heterogeneity and computational approaches for understanding autism","volume":"9","author":"Jacob","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41746-019-0191-0","article-title":"Artificial intelligence for precision medicine in neurodevelopmental disorders","volume":"2","author":"Uddin","year":"2019","journal-title":"NPJ Digit. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/14\/1176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:12:46Z","timestamp":1760109166000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/14\/1176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,10]]},"references-count":121,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["cells13141176"],"URL":"https:\/\/doi.org\/10.3390\/cells13141176","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,10]]}}}