Progressive divisions of multipotent neural progenitors generate late-born chandelier cells in the neocortex

Khadeejah T. Sultan, Wenying Angela Liu, Zhao-Lu Li, Zhongfu Shen, Zhizhong Li, Xin-Jun Zhang, Owen Dean, Jian Ma () and Song-Hai Shi ()
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Khadeejah T. Sultan: Memorial Sloan Kettering Cancer Center
Wenying Angela Liu: Memorial Sloan Kettering Cancer Center
Zhao-Lu Li: Tsinghua University
Zhongfu Shen: Tsinghua University
Zhizhong Li: Memorial Sloan Kettering Cancer Center
Xin-Jun Zhang: Memorial Sloan Kettering Cancer Center
Owen Dean: Memorial Sloan Kettering Cancer Center
Jian Ma: Tsinghua University
Song-Hai Shi: Memorial Sloan Kettering Cancer Center

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Diverse γ-aminobutyric acid (GABA)-ergic interneurons provide different modes of inhibition to support circuit operation in the neocortex. However, the cellular and molecular mechanisms underlying the systematic generation of assorted neocortical interneurons remain largely unclear. Here we show that NKX2.1-expressing radial glial progenitors (RGPs) in the mouse embryonic ventral telencephalon divide progressively to generate distinct groups of interneurons, which occupy the neocortex in a time-dependent, early inside-out and late outside-in, manner. Notably, the late-born chandelier cells, one of the morphologically and physiologically highly distinguishable GABAergic interneurons, arise reliably from continuously dividing RGPs that produce non-chandelier cells initially. Selective removal of Partition defective 3, an evolutionarily conserved cell polarity protein, impairs RGP asymmetric cell division, resulting in premature depletion of RGPs towards the late embryonic stages and a consequent loss of chandelier cells. These results suggest that consecutive asymmetric divisions of multipotent RGPs generate diverse neocortical interneurons in a progressive manner.

Date: 2018
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DOI: 10.1038/s41467-018-07055-7

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