The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells

Nat Neurosci. 2006 Jun;9(6):743-51. doi: 10.1038/nn1694. Epub 2006 May 7.


In the developing cerebral cortex, neurons are born on a predictable schedule. Here we show in mice that the essential timing mechanism is programmed within individual progenitor cells, and its expression depends solely on cell-intrinsic and environmental factors generated within the clonal lineage. Multipotent progenitor cells undergo repeated asymmetric divisions, sequentially generating neurons in their normal in vivo order: first preplate cells, including Cajal-Retzius neurons, then deep and finally superficial cortical plate neurons. As each cortical layer arises, stem cells and neuroblasts become restricted from generating earlier-born neuron types. Growth as neurospheres or in co-culture with younger cells did not restore their plasticity. Using short-hairpin RNA (shRNA) to reduce Foxg1 expression reset the timing of mid- but not late-gestation progenitors, allowing them to remake preplate neurons and then cortical-plate neurons. Our data demonstrate that neural stem cells change neuropotency during development and have a window of plasticity when restrictions can be reversed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Differentiation / physiology*
  • Cell Division / genetics
  • Cell Lineage / genetics*
  • Cell Movement / genetics
  • Cell Proliferation*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism
  • Down-Regulation / genetics
  • Extracellular Matrix Proteins / genetics
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Mice
  • Microscopy, Video
  • Nerve Tissue Proteins / genetics
  • Neuronal Plasticity / genetics
  • Neurons / cytology
  • Neurons / metabolism*
  • RNA Interference / physiology
  • Reelin Protein
  • Serine Endopeptidases / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Time Factors


  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Forkhead Transcription Factors
  • Foxg1 protein, mouse
  • Nerve Tissue Proteins
  • Reelin Protein
  • Serine Endopeptidases