Hatakeyama Jun, Kageyama Ryoichiro
Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Cereb Cortex. 2006 Jul;16 Suppl 1:i132-7. doi: 10.1093/cercor/bhj166.
In the developing nervous system, neural stem cells initially proliferate by a symmetric cell division and then undergo an asymmetric cell division, which makes one neuron (or neuronal precursor) and one progenitor. It remains to be determined how the switch from the symmetric to asymmetric cell divisions is regulated. Here, we found that Notch1 is expressed in the regions where neurogenesis occurs actively but not in the regions where neurogenesis does not yet occur. Furthermore, in Hes-mutant mice where neurogenesis is accelerated, Notch1 expression is also accelerated. Thus, Notch1 expression is negatively regulated by Hes genes and is spatiotemporally correlated with neurogenesis, suggesting that the neural stem cells that undergo asymmetric cell divisions express Notch1, whereas those that undergo symmetric cell divisions do not. We propose that initiation of Notch1 expression is one of the key features for switch from the symmetric to asymmetric cell divisions of neural stem cells and that this process is negatively regulated by Notch1-independent Hes genes.
在发育中的神经系统中，神经干细胞最初通过对称细胞分裂进行增殖，然后经历不对称细胞分裂，产生一个神经元（或神经元前体）和一个祖细胞。从对称细胞分裂向不对称细胞分裂的转变是如何被调控的，仍有待确定。在这里，我们发现Notch1在神经发生活跃的区域表达，但在尚未发生神经发生的区域不表达。此外，在神经发生加速的Hes突变小鼠中，Notch1的表达也加速。因此，Notch1的表达受Hes基因负调控，并且在时空上与神经发生相关，这表明经历不对称细胞分裂的神经干细胞表达Notch1，而经历对称细胞分裂的神经干细胞则不表达。我们提出，Notch1表达的起始是神经干细胞从对称细胞分裂向不对称细胞分裂转变的关键特征之一，并且这一过程受Notch1非依赖的Hes基因负调控。
