2025-08-28 マックス・プランク研究所
How do wrinkles form in the brain? Researchers compared brain sections of mice with different genetic changes. Using colored markers, they distinguished between the upper and lower layers of the developing cortex and highlighted different types of neurons. © MPI for Biological Intelligence / Seung Hee Chun
<関連情報>
- https://www.mpg.de/25267323/0829-psy-what-gives-our-brains-their-distinctive-wrinkles-155111-x
- https://www.nature.com/articles/s41467-025-62858-9
- https://www.cell.com/cell/fulltext/S0092-8674(17)30425-7
前駆細胞の増殖と接着制御による神経細胞移動の複合作用による大脳皮質の折り畳み Cortex folding by combined progenitor expansion and adhesion-controlled neuronal migration
Seung Hee Chun,Da Eun Yoon,D. Santiago Diaz Almeida,Mihail Ivilinov Todorov,Tobias Straub,Tobias Ruff,Wei Shao,Jianjun Yang,Gönül Seyit-Bremer,Yi-Ru Shen,Ali Ertürk,Daniel del Toro,Songhai Shi & Rüdiger Klein
Nature Communications Published:28 August 2025
DOI:https://doi.org/10.1038/s41467-025-62858-9
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.
FLRT接着分子を介した神経細胞移動制御による大脳皮質折り畳みの調節 Regulation of Cerebral Cortex Folding by Controlling Neuronal Migration via FLRT Adhesion Molecules
Daniel del Toro ∙ Tobias Ruff ∙ Erik Cederfjäll ∙ … ∙ Gönül Seyit-Bremer ∙ Víctor Borrell ∙ Rüdiger Klein
Cell Accepted: April 7, 2017
DOI:https://doi.org/10.1016/j.cell.2017.04.012
Highlights
- Flrt1/3 double-knockout mice develop macroscopic cortical sulci
- Cortex folding in mutant mice does not require progenitor cell amplification
- Absence of FLRT1/3 reduces intercellular adhesion and promotes immature neuron migration
- FLRT1/3 levels are low in the cortices of human embryos and future sulci of the ferret
Summary
The folding of the mammalian cerebral cortex into sulci and gyri is thought to be favored by the amplification of basal progenitor cells and their tangential migration. Here, we provide a molecular mechanism for the role of migration in this process by showing that changes in intercellular adhesion of migrating cortical neurons result in cortical folding. Mice with deletions of FLRT1 and FLRT3 adhesion molecules develop macroscopic sulci with preserved layered organization and radial glial morphology. Cortex folding in these mutants does not require progenitor cell amplification but is dependent on changes in neuron migration. Analyses and simulations suggest that sulcus formation in the absence of FLRT1/3 results from reduced intercellular adhesion, increased neuron migration, and clustering in the cortical plate. Notably, FLRT1/3 expression is low in the human cortex and in future sulcus areas of ferrets, suggesting that intercellular adhesion is a key regulator of cortical folding across species.
