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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 | Song-Hai Shi
Nature communications | 2018

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.

Pubmed ID: 30389944

Associated grants

  • Agency: NIDA NIH HHS, United States
    Id: R01 DA024681
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS105477
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH101382
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS085004

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