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Shin-ichi Ohnuma

Institute of Ophthalmology

Cell cycle and neural development

Co-ordination of the cell cycle and neural development

Co-ordination of cell cycle regulation with neural development is essential to achieve proper formation of the central nervous system (Ohnuma and Harris, 2003). Neural stem cells are maintained in a quiescent state and during neurogenesis they are converted to actively dividing neuroblasts. Upon receiving differentiation signals they generate postmitotic neurons and glial cells. If the cell cycle is impaired in any step, it results in defects of the central nervous system. However, very little is known about the mechanism of co-ordination.

We aim to determine the mechanisms of communication between the cell cycle and neural development through identification of key proteins using Xenopus retinogenesis as a model system. Our studies have identified several important proteins, including a cyclin dependent kinase inhibitor, p27Xic1, (Ohnuma et al., 1999) and a novel secreted protein, Tsukushi (Ohta et al., 2004). For example, p27Xic1 works as a co-ordinator of cell fate determination and cell cycle arrest at the late stage of neurogenesis. On the other hand, Tsukushi functions as a cell cycle inhibitor to keep neural stem cells quiet.


Currently these PhD projects are available in our lab.
1, Role of Tsukushi-mediated cell cycle inhibition in neural stem cell maintenance
2, Mechanism of p27Xic1-mediated neural cell fate determination
3, Role of the small leucine rich proteoglycan family in ocular development
If you are interested in our projects, please contact me directly (


Ohta, K., Lupo, G., Kuriyama, S., Keynes, R., Holt, C.E., Harris, W.A., Tanaka, H., and Ohnuma, S. (2004)
Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin.
Dev Cell 7, 347-358

Ohnuma, S., and Harris, W.A. (2003)
Neurogenesis and the cell cycle.
Neuron 40, 199-208

Ohnuma, S., Philpott, A., Wang, K., Holt, C.E., and Harris, W.A (1999)
p27Xic1, a Cdk inhibitor, promotes the determination of glial cells in Xenopus retina.


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