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