Unfolding the Folding Problem of the Cerebral Cortex: Movin’ and Groovin’

Itoh, Yoshio; Poulopoulos, Alexandros; Macklis, Jeffrey D.

doi:10.1016/j.devcel.2017.05.011

Cited by 1 publication

(1 citation statement)

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“…34 A widely accepted hypothesis suggests that cortex folding is driven by a combination of uneven progenitor expansion and divergent radial migration. 35 Yet, we still do not fully understand the logic behind how coordinated and simultaneous events like proliferation and divergent migration lead to the formation of sulci and gyri in the cortex. Here, we addressed this question by taking advantage of the Flrt1/3 dKO mouse line, which promotes divergent migration, and combined it with other genetic lines that induce progenitor expansion.…”

Section: Introductionmentioning

confidence: 99%

Cortex Folding by Combined Progenitor Expansion and Adhesion-Controlled Neuronal Migration

Chun,

Diaz Almeida,

Ivilinov Todorov

et al. 2024

Preprint

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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 find 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 results in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 results in enhanced formation of gyri. Single cell transcriptomics and simulations suggest that changes in adhesive properties of cortical neurons, their proportions and densities in the cortical plate, combined with lateral dispersion during their radial migration are important folding parameters. These results identify key developmental mechanisms that cooperate to promote cortical gyrification.

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Section: Introductionmentioning

confidence: 99%