Early dorsomedial tissue interactions regulate gyrification of distal neocortex

Victor V. Chizhikov (), Igor Y. Iskusnykh, Ekaterina Y. Steshina, Nikolai Fattakhov, Anne G. Lindgren, Ashwin S. Shetty, Achira Roy, Shubha Tole and Kathleen J. Millen ()
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Victor V. Chizhikov: University of Tennessee Health Science Center
Igor Y. Iskusnykh: University of Tennessee Health Science Center
Ekaterina Y. Steshina: University of Tennessee Health Science Center
Nikolai Fattakhov: University of Tennessee Health Science Center
Anne G. Lindgren: University of Chicago
Ashwin S. Shetty: Tata Institute of Fundamental Research
Achira Roy: Seattle Children’s Research Institute
Shubha Tole: Tata Institute of Fundamental Research
Kathleen J. Millen: Seattle Children’s Research Institute

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract The extent of neocortical gyrification is an important determinant of a species’ cognitive abilities, yet the mechanisms regulating cortical gyrification are poorly understood. We uncover long-range regulation of this process originating at the telencephalic dorsal midline, where levels of secreted Bmps are maintained by factors in both the neuroepithelium and the overlying mesenchyme. In the mouse, the combined loss of transcription factors Lmx1a and Lmx1b, selectively expressed in the midline neuroepithelium and the mesenchyme respectively, causes dorsal midline Bmp signaling to drop at early neural tube stages. This alters the spatial and temporal Wnt signaling profile of the dorsal midline cortical hem, which in turn causes gyrification of the distal neocortex. Our study uncovers early mesenchymal-neuroepithelial interactions that have long-range effects on neocortical gyrification and shows that lissencephaly in mice is actively maintained via redundant genetic regulation of dorsal midline development and signaling.

Date: 2019
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DOI: 10.1038/s41467-019-12913-z

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