Cortex folding by combined progenitor expansion and adhesion-controlled neuronal migration

Folding of the mammalian cerebral cortex into sulcal fissures and gyral peaks is the result of complex processes that are incompletely understood. Previously we showed that genetic deletion of Flrt1/3 adhesion molecules causes folding of the smooth mouse cortex into sulci resulting from increased lateral dispersion and faster neuron migration, without progenitor expansion. Here, we show in mice that combining the Flrt1/3 double knockout with an additional genetic deletion that causes progenitor expansion, greatly enhances cortex folding. Expansion of intermediate progenitors by deletion of Cep83 leads to a relative increase in Flrt-mutant neurons resulting in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 leads to a relative reduction in Flrt-mutant neurons resulting in enhanced formation of gyri. These results together with computational modeling identify key developmental mechanisms, such as adhesive properties, cell densities and migration of cortical neurons, that cooperate to promote cortical gyrification.

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Publication Details

Journal
Nature Communications
Published
2025-08-28
DOI
https://doi.org/10.1038/s41467-025-62858-9
Primary Topic
Axon Guidance and Neuronal Signaling
Type
article
Field-Weighted Citation Impact
0.00

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article

Cortex folding by combined progenitor expansion and adhesion-controlled neuronal migration

Tobias Ruff, Mihail Ivilinov Todorov, Daniel del Toro, Song‐Hai Shi et al.
Nature Communications
Axon Guidance and Neuronal Signaling
article

Cortex folding by combined progenitor expansion and adhesion-controlled neuronal migration

Tobias Ruff, Mihail Ivilinov Todorov, Daniel del Toro, Song‐Hai Shi, Seung Hee Chun, Ali Ertürk, G. Seyit-Bremer, Jianjun Yang, Rüdiger Klein, Tobias Straub, Da Eun Yoon, Yiru Shen, Wei Shao, D. Santiago Diaz Almeida
article en

Abstract

Folding of the mammalian cerebral cortex into sulcal fissures and gyral peaks is the result of complex processes that are incompletely understood. Previously we showed that genetic deletion of Flrt1/3 adhesion molecules causes folding of the smooth mouse cortex into sulci resulting from increased lateral dispersion and faster neuron migration, without progenitor expansion. Here, we show in mice that combining the Flrt1/3 double knockout with an additional genetic deletion that causes progenitor expansion, greatly enhances cortex folding. Expansion of intermediate progenitors by deletion of Cep83 leads to a relative increase in Flrt-mutant neurons resulting in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 leads to a relative reduction in Flrt-mutant neurons resulting in enhanced formation of gyri. These results together with computational modeling identify key developmental mechanisms, such as adhesive properties, cell densities and migration of cortical neurons, that cooperate to promote cortical gyrification.

Nature CommunicationsVol. 16(1)
Koç University (TR), McGovern Institute for Brain Research (US), Cornell University (US), Helmholtz Zentrum München (DE), ETH Zurich (CH), Institute for Biomedical Engineering (CH), Munich Cluster for Systems Neurology (DE), Chinese Institute for Brain Research (CN), Institut d'Investigacions Biomèdiques de Barcelona (ES), Max Planck Institute of Biochemistry (DE), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Max Planck Institute for Biological Intelligence, Universitat de Barcelona (ES), Ludwig-Maximilians-Universität München (DE)
Deutsche Forschungsgemeinschaft, Max-Planck-Gesellschaft
Openalex Percentile: Top 76%
Axon Guidance and Neuronal Signaling
DOIOpen Access PDFOpenAlex
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