[{"acknowledgement":"We thank F. Freeman, V. Voronin and M. Ladron de Guevara for technical assistance; A. Stichelberger and S. Liegenfeld for the management of our animal colony; M. Schunn, C. Gold and the Preclinical Facility team for technical assistance; C. Jansen and the Scientific Computing Facility for bioinformatics support and technical assistance; the Biomedical Sequencing Facility at CeMM for assistance with next-generation sequencing; and J. Lin and T. Krausgruber in the laboratory of C. Bock for support with flow cytometry; J. Kirchner for illustrating the multi-omics approach depicted in Fig. 1; and all members of the laboratory of G.N. for their support and discussions. This study was supported by the Scientific Service Units of ISTA through resources provided by the Imaging & Optics Facility and the Laboratory Support Facility. Bulk RNA-seq was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities, member of the Vienna BioCenter. This work was supported by a European Research Council Consolidator Grant (PR1028ERC02), by SFARI (PR1028SIM02) and by the Austrian Science Fund (PE1028W1232 and PR1028FG1803) to G.N. Open access funding provided by Institute of Science and Technology (IST Austria).","PlanS_conform":"1","status":"public","month":"06","date_updated":"2026-07-13T12:58:19Z","dataavailabilitystatement":"Single-nucleus multiomics data are available from the Gene Expression Omnibus (GSE328363). The mm10 reference genome was used for the alignment (refdata-cellranger-arc-mm10-2020-A-2.0.0, obtained from https://cf.10xgenomics.com/supp/cell-arc/refdata-cellranger-arc-mm10-2020-A-2.0.0.tar.gz). Single-cell data can be accessed and visualized through a CELLxGENE database (https://adameykolab.hifo.meduniwien.ac.at/cellxgene_public/filecrawl/.2026_Nature_Schwarz). Source data are provided with this paper. Scripts and analyses that support the main findings of this study are accessible in a GitHub repository (https://git.ista.ac.at/research-sofware/mouseome).","supplementarymaterial":"yes","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"researchdata_availability":"yes","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"year":"2026","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"day":"17","language":[{"iso":"eng"}],"corr_author":"1","publication":"Nature","oa_version":"Published Version","scopus_import":"1","department":[{"_id":"AnKi"},{"_id":"GaNo"},{"_id":"TiVo"},{"_id":"ScienComp"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"PreCl"}],"has_accepted_license":"1","ddc":["570"],"external_id":{"pmid":["42310454"]},"title":"Cortical development dynamics across autism spectrum disorder mouse models","OA_type":"hybrid","OA_place":"publisher","author":[{"full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A","last_name":"Schwarz"},{"full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","first_name":"Christoph","last_name":"Dotter"},{"first_name":"Sergey","last_name":"Isaev","full_name":"Isaev, Sergey"},{"last_name":"Lisi","first_name":"Michela","id":"39383c1b-d3eb-11ef-8d6c-c8cdf4e10c8c","full_name":"Lisi, Michela"},{"first_name":"Daniel","last_name":"Malzl","full_name":"Malzl, Daniel"},{"full_name":"Büschl, Christoph","id":"2a8c054c-0913-11ee-9159-f8ef515809ed","first_name":"Christoph","last_name":"Büschl"},{"full_name":"Ladstätter, Sabrina","first_name":"Sabrina","last_name":"Ladstätter"},{"first_name":"Bárbara","last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara"},{"first_name":"Matteo","last_name":"Barel","id":"8959927b-2236-11ed-bd6e-ea83d94ade0e","full_name":"Barel, Matteo"},{"orcid":"0000-0003-1843-3173","last_name":"Basilico","first_name":"Bernadette","full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"last_name":"Chintaluri","first_name":"Chaitanya","orcid":"0000-0003-4252-1608","id":"BA06AFEE-A4BA-11EA-AE5C-14673DDC885E","full_name":"Chintaluri, Chaitanya"},{"full_name":"Gorkiewicz, Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","first_name":"Sarah","last_name":"Gorkiewicz"},{"id":"3384113A-F248-11E8-B48F-1D18A9856A87","full_name":"Goudarzi, Mohammad","first_name":"Mohammad","last_name":"Goudarzi"},{"first_name":"Tereza","last_name":"Belinova","id":"0bf89b6a-d28b-11eb-8bd6-f43768e4d368","full_name":"Belinova, Tereza"},{"last_name":"Reichl","first_name":"Stephan","full_name":"Reichl, Stephan"},{"id":"dd6d52f2-c50d-11eb-9548-bcf0ff82b344","full_name":"Sendžikaitė, Gintarė","first_name":"Gintarė","last_name":"Sendžikaitė"},{"id":"b0bbee33-09f7-11eb-909c-8b358058d28a","full_name":"Arcot Jayaram, Satish","first_name":"Satish","last_name":"Arcot Jayaram","orcid":"0000-0002-2479-2669"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter","last_name":"Koppensteiner","first_name":"Peter","orcid":"0000-0002-3509-1948"},{"orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-3295-6181","last_name":"Vogels","first_name":"Tim P","full_name":"Vogels, Tim P","id":"CB6FF8D2-008F-11EA-8E08-2637E6697425"},{"last_name":"Menche","first_name":"Jörg","full_name":"Menche, Jörg"},{"full_name":"Adameyko, Igor","last_name":"Adameyko","first_name":"Igor"},{"full_name":"Kharchenko, Peter Vasili","id":"0095641e-7eb7-11f1-8665-aec51a2ab5e0","first_name":"Peter Vasili","last_name":"Kharchenko"},{"full_name":"Bock, Christoph","last_name":"Bock","first_name":"Christoph"},{"orcid":"0000-0002-7673-7178","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"date_created":"2026-07-13T09:47:21Z","project":[{"name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders","_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6","grant_number":"101044865"},{"name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers","_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","grant_number":"707964"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232"},{"name":"Neurobiology of anxiety in autism spectrum disorders","_id":"ebb38b5d-77a9-11ec-83b8-a42e08120a88","grant_number":"FG1803 49015"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"Despite the functional diversity of over 100 causal genes1,2,3, phenotypic convergence across models may reveal common neurobiological processes in autism spectrum disorder (ASD). Here we profiled 251 samples from 11 monogenic mouse models of ASD using single-nucleus multi-omic sequencing across three developmental stages, both sexes and two brain regions. Despite genetic heterogeneity, ASD-linked mutations converged on perturbations of the radial glial cell lineage. These alterations reflect a transient developmental delay rather than lasting lineage misspecification and resolve by postnatal stages. Molecularly, the largest transcriptional differences emerged in neurons at early postnatal stages. These changes included downregulation of synaptic and ion channel-related genes, consistent with homeostatic adaptation or delayed maturation. Network analysis showed molecular convergence across models within each developmental stage, suggesting that diverse mutations linked to ASD impinge on common, stage-specific processes. Convergence becomes less pronounced by postnatal day 14, highlighting the dynamic nature of ASD-associated changes. Cross-genotype heterogeneity is superimposed on stage-specific effects. Electrophysiology corroborated this pattern: mutants generally showed altered neuronal excitability and synaptic properties with model-specific nuances. Our study also highlighted sex-specific gene expression alterations, with female mice often displaying larger effect sizes than male mice. Together, our findings provide a comprehensive view of developmental cellular and molecular dynamics across models of ASD."}],"_id":"22295","pmid":1,"date_published":"2026-06-17T00:00:00Z","article_processing_charge":"Yes (via OA deal)","citation":{"ieee":"L. A. Schwarz <i>et al.</i>, “Cortical development dynamics across autism spectrum disorder mouse models,” <i>Nature</i>. Springer Nature, 2026.","mla":"Schwarz, Lena A., et al. “Cortical Development Dynamics across Autism Spectrum Disorder Mouse Models.” <i>Nature</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41586-026-10679-1\">10.1038/s41586-026-10679-1</a>.","ama":"Schwarz LA, Dotter C, Isaev S, et al. Cortical development dynamics across autism spectrum disorder mouse models. <i>Nature</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s41586-026-10679-1\">10.1038/s41586-026-10679-1</a>","ista":"Schwarz LA, Dotter C, Isaev S, Lisi M, Malzl D, Büschl C, Ladstätter S, Oliveira B, Barel M, Basilico B, Chintaluri C, Gorkiewicz S, Goudarzi M, Belinova T, Reichl S, Sendžikaitė G, Arcot Jayaram S, Koppensteiner P, Sommer CM, Vogels TP, Menche J, Adameyko I, Kharchenko PV, Bock C, Novarino G. 2026. Cortical development dynamics across autism spectrum disorder mouse models. Nature.","short":"L.A. Schwarz, C. Dotter, S. Isaev, M. Lisi, D. Malzl, C. Büschl, S. Ladstätter, B. Oliveira, M. Barel, B. Basilico, C. Chintaluri, S. Gorkiewicz, M. Goudarzi, T. Belinova, S. Reichl, G. Sendžikaitė, S. Arcot Jayaram, P. Koppensteiner, C.M. Sommer, T.P. Vogels, J. Menche, I. Adameyko, P.V. Kharchenko, C. Bock, G. Novarino, Nature (2026).","apa":"Schwarz, L. A., Dotter, C., Isaev, S., Lisi, M., Malzl, D., Büschl, C., … Novarino, G. (2026). Cortical development dynamics across autism spectrum disorder mouse models. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-026-10679-1\">https://doi.org/10.1038/s41586-026-10679-1</a>","chicago":"Schwarz, Lena A, Christoph Dotter, Sergey Isaev, Michela Lisi, Daniel Malzl, Christoph Büschl, Sabrina Ladstätter, et al. “Cortical Development Dynamics across Autism Spectrum Disorder Mouse Models.” <i>Nature</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41586-026-10679-1\">https://doi.org/10.1038/s41586-026-10679-1</a>."},"article_type":"original","quality_controlled":"1","doi":"10.1038/s41586-026-10679-1","publisher":"Springer Nature","oa":1,"main_file_link":[{"url":"https://doi.org/10.1038/s41586-026-10679-1","open_access":"1"}],"type":"journal_article","publication_status":"epub_ahead"}]