Cited by 716Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationCongenital heart defects research

Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains

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Imayoshi, Itaru, Sakamoto, Masayuki, Yamaguchi, Masahiro, Mori, Kensaku, Kageyama, Ryoichiro·2010·The Journal of Neuroscience

Abstract

Activation of Notch signaling induces the expression of transcriptional repressor genes such as Hes1 , leading to repression of proneural gene expression and maintenance of neural stem/progenitor cells. However, a requirement for Notch signaling in the telencephalon was not clear, because in Hes1;Hes3;Hes5 triple-mutant mice, neural stem/progenitor cells are depleted in most regions of the developing CNS, but not in the telencephalon. Here, we investigated a role for Notch signaling in the telencephalon by generating tamoxifen-inducible conditional knock-out mice that lack Rbpj , an intracellular signal mediator of all Notch receptors. When Rbpj was deleted in the embryonic brain, almost all telencephalic neural stem/progenitor cells prematurely differentiated into neurons and were depleted. When Rbpj was deleted in the adult brain, all neural stem cells differentiated into transit-amplifying cells and neurons. As a result, neurogenesis increased transiently, but 3 months later all neural stem cells were depleted and neurogenesis was totally lost. These results indicated an absolute requirement of Notch signaling for the maintenance of neural stem cells and a proper control of neurogenesis in both embryonic and adult brains.

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Crossref · 10.1523/jneurosci.4987-09.2010

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  • Notch signaling inhibits neural stem cell proliferation in zebrafish and mouse brain.

    “However, similar to the injured zebrafish retina, Notch signaling inhibits neural stem cell proliferation in the zebrafish and mouse brain (Chapouton et al., 2010; Imayoshi and Kageyama, 2011; Imayoshi et al., 2010).”

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Authors
Imayoshi, I., Sakamoto, M., Yamaguchi, M., Mori, K., & Kageyama, R.
Affiliations
  • Kyoto University (JP)
  • The University of Tokyo (JP)
Corresponding author
Kageyama, Ryoichiro
Venue
The Journal of Neuroscience
Published
2010-03-03
Volume
30
Issue
9
Pages
3489-3498
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2065569210
Cited by
716
References
58
Citations by year
2026: 17 · 2025: 31 · 2024: 34 · 2023: 39 · 2022: 60 · 2021: 46 · 2020: 54 · 2019: 47 · 2018: 45 · 2017: 45 · 2016: 39 · 2015: 42 · 2014: 58 · 2013: 51 · 2012: 52
FWCI
16.09
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology
  • Japan Society for the Promotion of Science (21240028)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords
Notch signaling, neural stem cells, neural stem/progenitor cells, RBPJ, Hes1, Hes5, telencephalon, neurogenesis, stem cell depletion, conditional knockout mice, adult brain, embryonic brain
MeSH terms
Aging, Animals, Cell Count, Mice, Transgenic, Nerve Regeneration, Neurons, Neurotoxins, Stem Cells, Telencephalon, Signal Transduction, Mice, Knockout, Gene Expression Regulation, Developmental, Cell Proliferation, Mice, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Receptors, Notch, Neurogenesis

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