Rhythmic gene expression in somite formation and neural development |
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Authors: | Ryoichiro Kageyama Yasutaka Niwa Hiromi Shimojo |
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Institution: | (1) Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan;(2) Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kyoto 606-8507, Japan |
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Abstract: | In mouse embryos, somite formation occurs every two hours, and this periodic event is regulated by a biological clock called
the segmentation clock, which involves cyclic expression of the basic helix-loop-helix gene Hes7. Hes7 expression oscillates by negative feedback and is cooperatively regulated by Fgf and Notch signaling. Both loss of
expression and sustained expression of Hes7 result in severe somite fusion, suggesting that Hes7 oscillation is required for
proper somite segmentation. Expression of a related gene, Hes1, also oscillates by negative feedback with a period of about two hours in many cell types such as neural progenitor cells.
Hes1 is required for maintenance of neural progenitor cells, but persistent Hes1 expression inhibits proliferation and differentiation of these cells, suggesting that Hes1 oscillation is required for their proper activities. Hes1 oscillation regulates cyclic expression of the proneural gene Neurogenin2 (Ngn2) and the Notch ligand Delta1, which in turn lead to maintenance of neural progenitor cells by mutual activation of Notch signaling. Taken together, these
results suggest that oscillatory expression with short periods (ultradian oscillation) plays an important role in many biological
events. |
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Keywords: | biological clock negative feedback segmentation clock ultradian oscillation |
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