TBR2 coordinates neurogenesis expansion and precise microcircuit organization via Protocadherin 19 in the mammalian cortex

Xiaohui Lv, Si-Qiang Ren, Xin-Jun Zhang, Zhongfu Shen, Tanay Ghosh, Anjin Xianyu, Peng Gao, Zhizhong Li, Susan Lin, Yang Yu, Qiangqiang Zhang, Matthias Groszer and Song-Hai Shi ()
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Xiaohui Lv: Memorial Sloan Kettering Cancer Center
Si-Qiang Ren: Memorial Sloan Kettering Cancer Center
Xin-Jun Zhang: Memorial Sloan Kettering Cancer Center
Zhongfu Shen: Tsinghua University
Tanay Ghosh: Sorbonne Université, Institut du Fer à Moulin
Anjin Xianyu: Memorial Sloan Kettering Cancer Center
Peng Gao: Memorial Sloan Kettering Cancer Center
Zhizhong Li: Memorial Sloan Kettering Cancer Center
Susan Lin: Memorial Sloan Kettering Cancer Center
Yang Yu: Memorial Sloan Kettering Cancer Center
Qiangqiang Zhang: Memorial Sloan Kettering Cancer Center
Matthias Groszer: Sorbonne Université, Institut du Fer à Moulin
Song-Hai Shi: Memorial Sloan Kettering Cancer Center

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Cerebral cortex expansion is a hallmark of mammalian brain evolution; yet, how increased neurogenesis is coordinated with structural and functional development remains largely unclear. The T-box protein TBR2/EOMES is preferentially enriched in intermediate progenitors and supports cortical neurogenesis expansion. Here we show that TBR2 regulates fine-scale spatial and circuit organization of excitatory neurons in addition to enhancing neurogenesis in the mouse cortex. TBR2 removal leads to a significant reduction in neuronal, but not glial, output of individual radial glial progenitors as revealed by mosaic analysis with double markers. Moreover, in the absence of TBR2, clonally related excitatory neurons become more laterally dispersed and their preferential synapse development is impaired. Interestingly, TBR2 directly regulates the expression of Protocadherin 19 (PCDH19), and simultaneous PCDH19 expression rescues neurogenesis and neuronal organization defects caused by TBR2 removal. Together, these results suggest that TBR2 coordinates neurogenesis expansion and precise microcircuit assembly via PCDH19 in the mammalian cortex.

Date: 2019
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DOI: 10.1038/s41467-019-11854-x

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