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

Qin Shen, Yue Wang, John T. Dimos, Christopher A. Fasano, Timothy N. Phoenix, Ihor R. Lemischka, Natalia B. Ivanova, Stefano Stifani, Edward E. Morrisey, Sally Temple

Research output: Contribution to journalArticlepeer-review

486 Scopus citations


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.

Original languageEnglish
Pages (from-to)743-751
Number of pages9
JournalNature Neuroscience
Issue number6
StatePublished - 16 Jun 2006
Externally publishedYes


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