{"doi":"10.1016/j.celrep.2025.116746","title":"Dual developmental effects of ARX poly-alanine mutations on human cortical excitatory and inhibitory neurons","abstract":"Infantile spasms (IS), a severe childhood epilepsy with an incidence of 1.6–4.5 per 10,000 live births, often lead to lifelong intellectual disability. Up to 5% of affected males carry mutations in the Aristaless-related homeobox ( ARX ) gene. The lack of human-specific models for developmental epilepsy limits progress, making organoids a promising alternative. We use human cortical organoids (COs) and ganglionic eminence organoids (GEOs) to model poly-alanine expansion (PAE) mutations in ARX . PAE mutations increase cortical progenitor proliferation and accelerate early cortical development. ARX expression is upregulated in patient-derived COs at 30 days in vitro (DIV), correlating with altered cell cycle gene expression. We observe enhanced, cell-autonomous interneuron migration, which is rescued by CXCR4 inhibition. ARX PAE assembloids exhibit early network hyperactivity. These findings highlight the utility of human brain organoids in uncovering ARX PAE -driven mechanisms and represent a critical step toward developing targeted therapies for IS and related developmental epilepsies.","journal":"Cell Reports","year":2025,"id":585951,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":477479,"name":"Parul Varma","orcid":"0000-0003-3313-7356","position":1,"is_corresponding":false},{"id":1328897,"name":"Sara Mirsadeghi","orcid":"0000-0001-7086-075X","position":2,"is_corresponding":false},{"id":1329406,"name":"J.M. Martín Caballero","orcid":null,"position":3,"is_corresponding":false},{"id":565593,"name":"Sergio Gamero-Alameda","orcid":null,"position":4,"is_corresponding":false},{"id":1328898,"name":"Ali Seif Amir Hosseini","orcid":"0000-0001-5891-8867","position":5,"is_corresponding":false},{"id":1329407,"name":"Marc Joshua Silvosa","orcid":null,"position":6,"is_corresponding":false},{"id":1329408,"name":"Drew Thodeson","orcid":null,"position":7,"is_corresponding":false},{"id":636974,"name":"Sonal Goswami","orcid":"0000-0003-2228-0325","position":8,"is_corresponding":false},{"id":565030,"name":"Zane R. Lybrand","orcid":"0000-0003-1543-8155","position":9,"is_corresponding":false},{"id":1328899,"name":"Michèle Giugliano","orcid":"0000-0003-2626-594X","position":10,"is_corresponding":false},{"id":798923,"name":"Christopher S. Navara","orcid":"0000-0001-5915-0327","position":11,"is_corresponding":false},{"id":473321,"name":"Jenny Hsieh","orcid":"0000-0003-0214-0771","position":12,"is_corresponding":false},{"id":576815,"name":"Vanesa Nieto‐Estévez","orcid":"0000-0002-7265-0593","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T02:59:24.273134Z","pmid":"41422506","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}