Nature Neuroscience 9, 743 - 751 (2006)
Published online: 7 May 2006; | doi:10.1038/nn1694
The timing of cortical neurogenesis is encoded within lineages of individual progenitor cellsQin Shen1, Yue Wang1, John T Dimos2, Christopher A Fasano1, Timothy N Phoenix1, Ihor R Lemischka2, Natalia B Ivanova2, Stefano Stifani3, Edward E Morrisey4
& Sally Temple11
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA. 2
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA. 3
Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada. 4
Department of Medicine and Molecular Cardiology Research Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Correspondence should be addressed to Qin Shen shenq@mail.amc.edu 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.
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