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Peer-reviewedCC BYNature

Developmental gene expression patterns driving species-specific cortical features

  • Awais Javed1
  • Lucía Gómez1,2
  • Veronica M. Pravatà3
  • Moein Sarhadi1
  • Quentin Lo Giudice1
  • Timéa Szalai1
  • Léa Aubert1,4
  • Théo Ribierre1,4
  • Laurent Nguyen5,6
  • Silvia Cappello3,7,8
  • Denis Jabaudon9,10,11
  • Esther Klingler12,13,14
14 affiliations
  1. 1Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland
  2. 2Institute for Applied Data Science and Finance, Bern University of Applied Sciences, Bern, Switzerland
  3. 3Division of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University (LMU), Munich, Germany
  4. 4NeuroNA Human Cellular Neuroscience Platform, Fondation Campus Biotech Geneva, Geneva, Switzerland
  5. 5Laboratory of Molecular Regulation of Neurogenesis, GIGA Institute, University of Liège, Liège, Belgium
  6. 6Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium
  7. 7Max Planck Institute of Psychiatry, Munich, Germany
  8. 8Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
  9. 9Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. [email protected]
  10. 10Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland. [email protected]
  11. 11Imagine Institute, Université Paris Cité, Paris, France. [email protected]
  12. 12Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. [email protected]
  13. 13KU Leuven Department of Neurosciences, Leuven Brain Institute, Leuven Institute for Single Cell Omics, Leuven, Belgium. [email protected]
  14. 14VIB Center for Neuroscience Leuven, Leuven, Belgium. [email protected]
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Abstract

. These structural differences may reflect evolutionary changes in the developmental expression of shared genes. Here, to investigate this possibility, we used machine vision to identify and compare cell-type-specific gene expression patterns in the developing mouse and human neocortex, and in human cortical organoids. Using this approach, we identified genes with evolutionarily conserved or divergent transcriptional regulation, revealing species-specific cyto-temporal gene expression patterns. Among such genes, the transcription factor gene JUNB showed mutually exclusive expression in human progenitors and mouse neurons. Through cell-type-specific gain- and loss-of-function experiments in mice and human cortical organoids, we show that JUNB bidirectionally controls human cortical features, including progenitor proliferation rates, neuronal production timing and total neuronal output. We identify IRF1 as a human radial glia-specific regulator that, when expressed in mouse radial glia, activates JUNB and recruits human-like gene regulatory networks, demonstrating cross-species activation of poised developmental programmes. Together, these findings reveal how cyto-temporal regulation of shared genes drives species-specific cortical features, and provide a molecular framework for understanding and manipulating these evolutionary programmes.

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Cite

BibTeXRIS
BibTeX
@article{javed2026developmental,
  title = {{Developmental gene expression patterns driving species-specific cortical features}},
  author = {Awais Javed and Lucía Gómez and Veronica M. Pravatà and Moein Sarhadi and Quentin Lo Giudice and Timéa Szalai and Léa Aubert and Théo Ribierre and Laurent Nguyen and Silvia Cappello and Denis Jabaudon and Esther Klingler},
  journal = {Nature},
  year = {2026},
  month = may,
  doi = {10.1038/s41586-026-10491-x},
  url = {https://doi.org/10.1038/s41586-026-10491-x},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Developmental gene expression patterns driving species-specific cortical features
AU  - Awais Javed
AU  - Lucía Gómez
AU  - Veronica M. Pravatà
AU  - Moein Sarhadi
AU  - Quentin Lo Giudice
AU  - Timéa Szalai
AU  - Léa Aubert
AU  - Théo Ribierre
AU  - Laurent Nguyen
AU  - Silvia Cappello
AU  - Denis Jabaudon
AU  - Esther Klingler
PY  - 2026
DA  - 2026/05/13
JO  - Nature
DO  - 10.1038/s41586-026-10491-x
UR  - https://doi.org/10.1038/s41586-026-10491-x
AB  - . These structural differences may reflect evolutionary changes in the developmental expression of shared genes. Here, to investigate this possibility, we used machine vision to identify and compare cell-type-specific gene expression patterns in the developing mouse and human neocortex, and in human cortical organoids. Using this approach, we identified genes with evolutionarily conserved or divergent transcriptional regulation, revealing species-specific cyto-temporal gene expression patterns. Among such genes, the transcription factor gene JUNB showed mutually exclusive expression in human progenitors and mouse neurons. Through cell-type-specific gain- and loss-of-function experiments in mice and human cortical organoids, we show that JUNB bidirectionally controls human cortical features, including progenitor proliferation rates, neuronal production timing and total neuronal output. We identify IRF1 as a human radial glia-specific regulator that, when expressed in mouse radial glia, activates JUNB and recruits human-like gene regulatory networks, demonstrating cross-species activation of poised developmental programmes. Together, these findings reveal how cyto-temporal regulation of shared genes drives species-specific cortical features, and provide a molecular framework for understanding and manipulating these evolutionary programmes.
SN  - 0028-0836
SN  - 1476-4687
ER  -