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

Nature Neuroscience volume 11, pages 1247–1251 (2008)Cite this article

Abstract

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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Figure 1: Notch signaling pathway.
Figure 2: Two models for lateral inhibition-mediated formation of salt-and-pepper patterns.
Figure 3: Salt-and-pepper patterns of Dll1 expression in the developing mouse brain.
Figure 4: Oscillator networks in neural progenitors.

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Acknowledgements

This work was supported by the grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Uehara Memorial Foundation. H.S. and I.I. were supported by the 21st Century Center of Excellence Program of the Ministry of Education, Culture, Sports, Science and Technology of Japan and Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.

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Authors and Affiliations

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

    Ryoichiro Kageyama, Toshiyuki Ohtsuka, Hiromi Shimojo & Itaru Imayoshi

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  1. Ryoichiro Kageyama
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Correspondence to Ryoichiro Kageyama.

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Kageyama, R., Ohtsuka, T., Shimojo, H. et al. Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition. Nat Neurosci 11, 1247–1251 (2008). https://doi.org/10.1038/nn.2208

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