article epub_ahead yes Lena A Schwarz author 29A8453C-F248-11E8-B48F-1D18A9856A87 Christoph Dotter author 4C66542E-F248-11E8-B48F-1D18A9856A870000-0002-9033-9096 Sergey Isaev author Michela Lisi author 39383c1b-d3eb-11ef-8d6c-c8cdf4e10c8c Daniel Malzl author Christoph Büschl author 2a8c054c-0913-11ee-9159-f8ef515809ed Sabrina Ladstätter author Bárbara Oliveira author 3B03AA1A-F248-11E8-B48F-1D18A9856A87 Matteo Barel author 8959927b-2236-11ed-bd6e-ea83d94ade0e Bernadette Basilico author 36035796-5ACA-11E9-A75E-7AF2E56974250000-0003-1843-3173 Chaitanya Chintaluri author BA06AFEE-A4BA-11EA-AE5C-14673DDC885E0000-0003-4252-1608 Sarah Gorkiewicz author f141a35d-15a9-11ec-9fb2-fef6becc7b6f Mohammad Goudarzi author 3384113A-F248-11E8-B48F-1D18A9856A87 Tereza Belinova author 0bf89b6a-d28b-11eb-8bd6-f43768e4d368 Stephan Reichl author Gintarė Sendžikaitė author dd6d52f2-c50d-11eb-9548-bcf0ff82b344 Satish Arcot Jayaram author b0bbee33-09f7-11eb-909c-8b358058d28a0000-0002-2479-2669 Peter Koppensteiner author 3B8B25A8-F248-11E8-B48F-1D18A9856A870000-0002-3509-1948 Christoph M Sommer author 4DF26D8C-F248-11E8-B48F-1D18A9856A870000-0003-1216-9105 Tim P Vogels author CB6FF8D2-008F-11EA-8E08-2637E66974250000-0003-3295-6181 Jörg Menche author Igor Adameyko author Peter Vasili Kharchenko author 0095641e-7eb7-11f1-8665-aec51a2ab5e0 Christoph Bock author Gaia Novarino author 3E57A680-F248-11E8-B48F-1D18A9856A870000-0002-7673-7178 AnKi department GaNo department TiVo department ScienComp department GradSch department Bio department PreCl department Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders project Critical windows and reversibility of ASD associated with mutations in chromatin remodelers project Molecular Drug Targets project Neurobiology of anxiety in autism spectrum disorders project 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. https://creativecommons.org/licenses/by/4.0/ Springer Nature2026 eng 0028-0836 1476-4687 4231045410.1038/s41586-026-10679-1 L. A. Schwarz <i>et al.</i>, “Cortical development dynamics across autism spectrum disorder mouse models,” <i>Nature</i>. Springer Nature, 2026. 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). 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. 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>. 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>. 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> 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> 222952026-07-13T09:47:21Z2026-07-13T12:58:19Z