The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells
The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells
复制标题
DOI：
10.1038/nn1694
复制
发表时间：
2006-06-01
影响因子：
25
通讯作者：
Temple, Sally
中科院分区：
文献类型：
--
作者：
Shen, Qin;Wang, Yue;Temple, Sally
在发育中的大脑皮层中，神经元是按照可预测的时间表出生的。在这里，我们在小鼠中显示，基本的定时机制是在个体祖细胞内编程的，其表达仅取决于克隆谱系内产生的细胞内在和环境因素。多能祖细胞经历重复的不对称分裂，以其正常的体内顺序依次产生神经元：首先是前板细胞，包括Cajal-Retzius神经元，然后是深层和最后是表层皮质板神经元。随着每一层皮层的出现，干细胞和神经母细胞在生成早期出生的神经元类型方面受到限制。作为神经球生长或与年轻细胞共培养不能恢复其可塑性。使用短发夹RNA（shRNA）来减少Foxg 1的表达，重新设定了妊娠中期而不是妊娠晚期祖细胞的时间，使它们能够重新制造前板神经元，然后是皮质板神经元。我们的数据表明，神经干细胞在发育过程中改变神经潜能，并且当限制可以逆转时具有可塑性窗口。
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.