Abstract
The activator-type basic helix-loop-helix (bHLH) genes such as Mash1 and Neurogenin2 (Ngn2) promote neuronal differentiation and induce expression of Notch ligands such as Delta1, which activate Notch signaling of neighboring cells. Activation of Notch signaling induces expression of the repressor-type bHLH genes such as Hes1 and Hes5, which maintain neural progenitor cells by antagonizing activator-type bHLH genes. Thus, differentiating neurons keep their neighboring cells as neural progenitor cells via Notch signaling. How, then, are neural progenitor cells maintained before formation of such neurons? A recent study revealed that Hes1 expression occurs rhythmically in neural progenitor cells, and that Ngn2 and Delta1 are also expressed in an oscillatory manner by these cells. Inhibition of Notch signaling, a condition known to induce neuronal differentiation, leads to down-regulation of Hes1 and sustained up-regulation of Ngn2 and Delta1, suggesting that Hes1 oscillation regulates Ngn2 and Delta1 oscillations. It is likely that Delta1 oscillations reciprocally activate Notch signaling between neighboring neural progenitor cells. These results also suggest that oscillatory expression of Ngn2 is not sufficient but sustained up-regulation is required for neuronal differentiation and that Ngn2 oscillation is advantageous for activation of Notch signaling by inducing Delta1 expression without promoting neuronal differentiation.
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Abbreviations
- bHLH:
-
basic helix-loop-helix
- GABA:
-
γ-aminobutyric acid
- Ngn2:
-
Neurogenin 2
- NICD:
-
Notch intracellular domain
- Stat3-P:
-
Phosphorylated Stat3
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Acknowledgments
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. was supported by the twenty-first 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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Shimojo, H., Ohtsuka, T., Kageyama, R. (2010). Rhythmic Expression of Notch Signaling in Neural Progenitor Cells. In: Ulrich, H. (eds) Perspectives of Stem Cells. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3375-8_10
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