Folding of the Cerebral Cortex Requires Cdk5 in Upper-Layer Neurons in Gyrencephalic Mammals

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Yohei Shinmyo, Yukari Terashita, Tung Anh Dinh Duong, Toshihide Horiike, Muneo Kawasumi, Kazuyoshi Hosomichi, Atsushi Tajima, Hiroshi Kawasaki
Folds in the cerebral cortex in mammals are believed to be key structures for accommodating increased cortical neurons in the cranial cavity. However, the mechanisms underlying cortical folding remain largely unknown, mainly because genetic manipulations for the gyrencephalic brain have been unavailable. By combining in utero electroporation and the CRISPR/Cas9 system, we succeeded in efficient gene knockout of Cdk5, which is mutated in some patients with classical lissencephaly, in the gyrencephalic brains of ferrets. We show that Cdk5 knockout in the ferret cerebral cortex markedly impaired cortical folding. Furthermore, the results obtained from the introduction of dominant-negative Cdk5 into specific cortical layers suggest that Cdk5 function in upper-layer neurons is more important for cortical folding than that in lower-layer neurons. Cdk5 inhibition induced severe migration defects in cortical neurons. Taken together, our findings suggest that the appropriate positioning of upper-layer neurons is critical for cortical folding.

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Shinmyo et al. describe a highly efficient gene knockout method for the folded cerebral cortex of ferrets using the CRISPR/Cas9 system. Loss-of-function studies of the Cdk5 gene suggest that appropriate positioning of upper-layer neurons is crucial for cortical folding.


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