---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '22295'
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.'
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
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).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Lena A
  full_name: Schwarz, Lena A
  id: 29A8453C-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- first_name: Sergey
  full_name: Isaev, Sergey
  last_name: Isaev
- first_name: Michela
  full_name: Lisi, Michela
  id: 39383c1b-d3eb-11ef-8d6c-c8cdf4e10c8c
  last_name: Lisi
- first_name: Daniel
  full_name: Malzl, Daniel
  last_name: Malzl
- first_name: Christoph
  full_name: Büschl, Christoph
  id: 2a8c054c-0913-11ee-9159-f8ef515809ed
  last_name: Büschl
- first_name: Sabrina
  full_name: Ladstätter, Sabrina
  last_name: Ladstätter
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Matteo
  full_name: Barel, Matteo
  id: 8959927b-2236-11ed-bd6e-ea83d94ade0e
  last_name: Barel
- first_name: Bernadette
  full_name: Basilico, Bernadette
  id: 36035796-5ACA-11E9-A75E-7AF2E5697425
  last_name: Basilico
  orcid: 0000-0003-1843-3173
- first_name: Chaitanya
  full_name: Chintaluri, Chaitanya
  id: BA06AFEE-A4BA-11EA-AE5C-14673DDC885E
  last_name: Chintaluri
  orcid: 0000-0003-4252-1608
- first_name: Sarah
  full_name: Gorkiewicz, Sarah
  id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f
  last_name: Gorkiewicz
- first_name: Mohammad
  full_name: Goudarzi, Mohammad
  id: 3384113A-F248-11E8-B48F-1D18A9856A87
  last_name: Goudarzi
- first_name: Tereza
  full_name: Belinova, Tereza
  id: 0bf89b6a-d28b-11eb-8bd6-f43768e4d368
  last_name: Belinova
- first_name: Stephan
  full_name: Reichl, Stephan
  last_name: Reichl
- first_name: Gintarė
  full_name: Sendžikaitė, Gintarė
  id: dd6d52f2-c50d-11eb-9548-bcf0ff82b344
  last_name: Sendžikaitė
- first_name: Satish
  full_name: Arcot Jayaram, Satish
  id: b0bbee33-09f7-11eb-909c-8b358058d28a
  last_name: Arcot Jayaram
  orcid: 0000-0002-2479-2669
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Tim P
  full_name: Vogels, Tim P
  id: CB6FF8D2-008F-11EA-8E08-2637E6697425
  last_name: Vogels
  orcid: 0000-0003-3295-6181
- first_name: Jörg
  full_name: Menche, Jörg
  last_name: Menche
- first_name: Igor
  full_name: Adameyko, Igor
  last_name: Adameyko
- first_name: Peter Vasili
  full_name: Kharchenko, Peter Vasili
  id: 0095641e-7eb7-11f1-8665-aec51a2ab5e0
  last_name: Kharchenko
- first_name: Christoph
  full_name: Bock, Christoph
  last_name: Bock
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  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>
  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>.
  ieee: L. A. Schwarz <i>et al.</i>, “Cortical development dynamics across autism
    spectrum disorder mouse models,” <i>Nature</i>. Springer Nature, 2026.
  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.
  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>.
  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).
corr_author: '1'
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).
date_created: 2026-07-13T09:47:21Z
date_published: 2026-06-17T00:00:00Z
date_updated: 2026-07-13T12:58:19Z
day: '17'
ddc:
- '570'
department:
- _id: AnKi
- _id: GaNo
- _id: TiVo
- _id: ScienComp
- _id: GradSch
- _id: Bio
- _id: PreCl
doi: 10.1038/s41586-026-10679-1
external_id:
  pmid:
  - '42310454'
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41586-026-10679-1
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6
  grant_number: '101044865'
  name: Toward an understanding of the brain interstitial system and the extracellular
    proteome in health and autism spectrum disorders
- _id: 9B91375C-BA93-11EA-9121-9846C619BF3A
  grant_number: '707964'
  name: Critical windows and reversibility of ASD associated with mutations in chromatin
    remodelers
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232
  name: Molecular Drug Targets
- _id: ebb38b5d-77a9-11ec-83b8-a42e08120a88
  grant_number: FG1803 49015
  name: Neurobiology of anxiety in autism spectrum disorders
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Cortical development dynamics across autism spectrum disorder mouse models
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...