Human-specific morphoregulatory signatures in basal radial glia characterise neocortex evolution
Abstract As the seat of our cognition, the human neocortex is an object of immense fascination. Human neocortex expansion during evolution has been attributed to an increase in the proliferative capacity of neural progenitor cells during development, particularly basal radial glia. Despite their evolutionary relevance, the genomic changes driving human basal radial glia biology remain uncharacterised. We use comparative chromatin and transcriptional profiling of neural progenitor cells isolated from gorilla, chimpanzee and human cerebral organoids to identify cis-regulatory elements that have gained activity in humans. Focusing specifically on basal radial glia, we discover that morphoregulatory enhancer activity and gene expression signatures distinguish human basal radial glia from other great apes. Functional analysis of the morphoregulatory genes FAM107A and CNGA3 in human organoids reveals that these genes contribute to the morphological complexity of human basal radial glia. Taken together, our inter-species comparison of basal radial glia suggests that human-specific morphoregulatory signatures characterise neocortex evolution.
Authors
- Boyan Bonev (ORCID: https://orcid.org/0000-0002-7502-9399)
- Takashi Namba (ORCID: https://orcid.org/0000-0003-4875-666X)
- Jula Peters (ORCID: https://orcid.org/0000-0002-0770-8891)
- Christina Eugster Oegema (ORCID: https://orcid.org/0000-0002-8895-0726)
- Katherine R. Long (ORCID: https://orcid.org/0000-0003-0660-2486)
- Cahit Birdir (ORCID: https://orcid.org/0000-0003-0242-1178)
- Theresa M. Schütze (ORCID: https://orcid.org/0000-0002-4257-2192)
- Mareike Albert (ORCID: https://orcid.org/0000-0001-9855-9344)
- Annika Kolodziejczyk (ORCID: https://orcid.org/0000-0003-4447-2563)
- Razvan P. Derihaci (ORCID: https://orcid.org/0000-0001-9357-5230)
- Nora Ditzer (ORCID: https://orcid.org/0000-0002-7157-0372)
- Pauline Wimberger (ORCID: https://orcid.org/0000-0002-7380-577X)
- Maximilian Krause (ORCID: https://orcid.org/0000-0002-7715-1160)
- Nereo Kalebic (ORCID: https://orcid.org/0000-0002-8445-2906)
- Ilaria Chiaradia (ORCID: https://orcid.org/0000-0002-9529-4464)
- Madeline A. Lancaster (ORCID: https://orcid.org/0000-0003-2324-8853)
- Silvia Vangelisti (ORCID: https://orcid.org/0000-0002-0747-6293)
- Seiya Yamada (ORCID: https://orcid.org/0000-0001-7528-7489)
- Vida Kufrin (ORCID: https://orcid.org/0009-0002-2431-7654)
- Ulrich Martin (ORCID: https://orcid.org/0000-0003-1058-4540)
- Alexander Arthur Wurm (ORCID: https://orcid.org/0000-0003-0065-9481)
- Emanuele Capra (ORCID: https://orcid.org/0009-0005-0224-9728)
- Jeong-Eun Lee
Institutions
- University of Helsinki (FI)
- Fujita Health University (JP)
- MRC Laboratory of Molecular Biology (GB)
- King's College London (GB)
- Helmholtz-Zentrum Dresden-Rossendorf (DE)
- University Hospital Heidelberg (DE)
- Helmholtz Zentrum München (DE)
- Medizinische Hochschule Hannover (DE)
- Human Technopole (IT)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- University Hospital Carl Gustav Carus (DE)
- Nationales Centrum für Tumorerkrankungen Dresden (DE)
- HiLIFE – Elämäntieteiden Instituutti
- MRC Centre for Neurodevelopmental Disorders (GB)
- Center for Regenerative Therapies Dresden (DE)
- DRESDEN-concept Genome Center (DE)
- Center for Molecular and Cellular Bioengineering (DE)
- Technische Universität Dresden (DE)
- Epigenomics (Germany) (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-10-09
- DOI
- https://doi.org/10.1038/s41467-026-78474-0
- Primary Topic
- Neurogenesis and neuroplasticity mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00