Notch1 Expression Is Spatiotemporally Correlated with Neurogenesis and Negatively Regulated by Notch1-Independent Hes Genes in the Developing Nervous System
Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan, 1 Current address: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan
Address correspondence to Ryoichiro Kageyama, Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan. Email: rkageyam{at}virus.kyoto-u.ac.jp.
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.
Key Words: asymmetric cell division • delta • neural stem cell • neuroepithelial cell • radial glial cell