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Nat Neurosci. 2008 Nov;11(11):1247-51. doi: 10.1038/nn.2208.

Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition.

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  • 1Institute for Virus Research, Kyoto University and Japan Science and Technology Agency, CREST, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan.


In the developing mammalian nervous system, neural progenitor cells first express the Notch effector Hes1 at variable levels and then proneural genes and Notch ligands in salt-and-pepper patterns. Recent real-time imaging analysis indicates that Hes1 expression in these cells oscillates with a period of about 2-3 h. Furthermore, the proneural gene Neurogenin-2 (Ngn2) and the Notch ligand gene Deltalike-1 (Dll1) are expressed cyclically in neural progenitor cells under the control of Hes1 oscillation but are expressed continuously in postmitotic neurons, which lose Hes1 expression. Hes1-driven Ngn2 and Dll1 oscillations seem to be advantageous for maintenance of a group of cells in an undifferentiated state by mutual activation of Notch signaling. This dynamic mode of gene expression would require a revision of the traditional view of how Notch-mediated lateral inhibition operates in the developing mammalian nervous system.

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