It is printed in the A4 size.To the laboratory site

 - Institute for Virus Research
Growth Regulation
Department of Cell Biology
It is really fascinating and exciting to see the process where a fertilized egg develops into a complicated embryo. How does each cell in embryos know its own position and role? How do many events proceed coordinately at the right time and the right place? Many things remain to be solved in developmental biology. We are challenging these difficult but fascinating problems of developmental biology. The results from this research will be useful for the future regeneration therapy. We hope many students will join us to challenge these problems.

  Ryoichiro Kageyama, M.D., Ph.D.
Research and Education
The research interest of this laboratory is to understand the molecular mechanism of cell differentiation and organogenesis. Particularly, we are interested in transcription factors that regulate neural development. Our research strategies are misexpressing the genes with retrovirus and electroporation (gain-of-function study) and generating knock-out mice (loss-of-function study). We are focusing on basic helix-loop-helix (bHLH) transcription factors such as the repressor-type bHLH factors Hes1 and Hes5 and the activator-type bHLH factors Math, Mash, NeuroD and Neurogenin. During neural development, the following three major steps occur sequentially: (1) maintenance of neural stem cells, (2) neurogenesis and (3) gliogenesis. We have demonstrated that the steps (1) and (3) are regulated by the repressor-type bHLH factors while the step (2) is regulated by the activator-type bHLH factors. These findings will be useful for the future regeneration therapy.
We are also interested in biological clocks that regulate embryogenesis. We have recently found that the bHLH factors Hes1 and Hes7 act as two-hour cycle biological clocks in embryos. Hes7 regulates the timing of somite segmentation, which occurs every two hours in mice. We are now studying what developmental processes, besides somite segmentation, these biological clocks regulate. This research will open the new field “Developmental Chronobiology”.
Regarding education, we are committed to providing graduate students with the highest quality of research environment and thereby educating them to be the scientists who play an essential role in international societies. Students with various backgrounds study Developmental Biology from the beginning and join the research project described above. They have the opportunity to present and discuss their results in domestic and international meetings and to publish them in international journals.

Growth Regulation
Institute for Virus Research
Professor Ryoichiro Kageyama

Toshiyuki Ohtsuka

Taeko Kobayashi
TEL +81-75-751-4011
FAX +81-75-751-4807
bHLH factors regulate three steps of neural development.
The repressor-type bHLH factors Hes1 and Hes5 are essential for maintenance of neural stem cells. (Upper) In the absence of Hes1 and Hes5, neurons are prematurely differentiated and neural stem cells are not maintained. (Lower) Hes1;Hes5 double-null neural stem cells do not grow well and form only small neurospheres.
Hes1 and Hes7 as two-hour cycle biological clocks. Hes1 and Hes7 expression oscillates autonomously by negative feedback. These biological clocks regulate the progress of embryogenesis.
Recent Publications
1. Niwa, Y., Shimojo, H., Isomura, A., Gonzez, A., Miyachi, H., and Kageyama, R. (2011) Different types of oscillations in Notch and Fgf signaling regulate the spatiotemporal periodicity of somitogenesis. Genes & Dev. 25, 1115-1120.
2. Kobayashi, T., Mizuno, H., Imayoshi, I., Furusawa, C., Shirahige, K., and Kageyama, R. (2009) The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells. Genes & Dev. 23, 1870-1875.
3. Kageyama, R., Ohtsuka, T., Shimojo, H., and Imayoshi, I. (2008) Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition. Nature Neurosci. 11, 1247-1251.
4. Imayoshi, I., Sakamoto, M., Ohtsuka, T., Takao, K., Miyakawa, T., Yamaguchi, M., Mori, K., Ikeda, T., Itohara, S., and Kageyama, R. (2008) Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nature Neurosci. 11, 1153-1161.
5. Shimojo, H., Ohtsuka, T., and Kageyama, R. (2008) Oscillations in Notch signaling regulate maintenance of neural progenitors. Neuron 58, 52-64.