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

Nat Commun. 2018 Nov 2;9(1):4595. doi: 10.1038/s41467-018-07055-7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Asymmetric Cell Division
  • Cell Adhesion Molecules / metabolism
  • Cell Cycle Proteins
  • Cell Division*
  • Interneurons / cytology
  • Median Eminence / cytology
  • Neocortex / cytology*
  • Neural Stem Cells / cytology*
  • Neurogenesis*
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Preoptic Area / cytology
  • Staining and Labeling
  • Thyroid Nuclear Factor 1 / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Nkx2-1 protein, mouse
  • Pard3 protein, mouse
  • Thyroid Nuclear Factor 1