title: The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells.
abstract: 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.
authors: Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA. shenq@mail.amc.edu
authors: Qin
authors: Q
authors: Shen
authors: Yue
authors: Y
authors: Wang
authors: John T
authors: JT
authors: Dimos
authors: Christopher A
authors: CA
authors: Fasano
authors: Timothy N
authors: TN
authors: Phoenix
authors: Ihor R
authors: IR
authors: Lemischka
authors: Natalia B
authors: NB
authors: Ivanova
authors: Stefano
authors: S
authors: Stifani
authors: Edward E
authors: EE
authors: Morrisey
authors: Sally
authors: S
authors: Temple