Journal Article

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

del Toro, Daniel, Shi, Songhai, Ertürk, Ali, Shao, Wei, Shen, Yi-Ru, Straub, Tobias, Yoon, Da Eun, Todorov, Mihail Ivilinov, Chun, Seung Hee, Yang, Jianjun, Seyit-Bremer, Gönül, Klein, Rüdiger, Ruff, Tobias, Diaz Almeida, D. Santiago

2025

Overview

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. The complex processes guiding mammalian cortical folding are incompletely understood. Here authors report that cortical folding was enhanced in mice by combining mutations affecting neuron adhesion and progenitor expansion, producing both sulci and gyri.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14/32 / 38 / 38/35 / 45/91 / 631/136/2091 / 631/378/2571/1696 / 64/60 / 82/51 / Ablation / Adhesion / Animals / Cell Adhesion / Cell adhesion & migration / Cell growth / Cell migration / Cell Movement - physiology / Cerebral cortex / Cerebral Cortex - cytology / Cerebral Cortex - embryology / Cerebral Cortex - growth & development / Cerebral Cortex - metabolism / Deletion / Fibroblast growth factor 10 / Fibroblast Growth Factor 10 - genetics / Fibroblast Growth Factor 10 - metabolism / Folding / Genotype & phenotype / Humanities and Social Sciences / Mammals / Mice / Mice, Knockout / multidisciplinary / Mutants / Neural stem cells / Neural Stem Cells - cytology / Neural Stem Cells - metabolism / Neurons / Neurons - cytology / Neurons - metabolism / Neurons - physiology / Science / Science (multidisciplinary)