GSK-3 is a master regulator of neural progenitor homeostasis
Open accessAbstract
The development of the brain requires the exquisite coordination of progenitor proliferation and differentiation to achieve complex circuit assembly. It has been suggested that glycogen synthase kinase 3 (GSK-3) acts as an integrating molecule for multiple proliferation and differentiation signals because of its essential role in the RTK, Wnt and Shh signaling pathways. We created conditional mutations that deleted both the alpha and beta forms of GSK-3 in mouse neural progenitors. GSK-3 deletion resulted in massive hyperproliferation of neural progenitors along the entire neuraxis. Generation of both intermediate neural progenitors and postmitotic neurons was markedly suppressed. These effects were associated with the dysregulation of beta-catenin, Sonic Hedgehog, Notch and fibroblast growth factor signaling. Our results indicate that GSK-3 signaling is an essential mediator of homeostatic controls that regulate neural progenitors during mammalian brain development.
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Gsk3 knockout resulted in expanded RGC pools, fewer IPCs, reduced cortical thickness and increased ventricular apical surface length.
“This resulted in expanded RGC pools, fewer IPCs, reduced cortical thickness and increased ventricular apical surface length [102].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [102]
As a result of Gsk3 knockout, RGCs were locked in a proliferative state with attenuated neurogenesis.
“As a result, RGCs were locked in proliferative state with attenuated neurogenesis [102].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [102]
RGCs in a mouse model of Gsk3 knockout show more highly active β-catenin and Notch pathways.
“RGCs in a mouse model of Gsk3 knockout, a major convergence point of the signaling pathways (Fig. 6), show more highly active β-catenin and Notch pathways [102].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [102]
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- Authors
- Kim, W.-Y., Wang, X., Wu, Y., Doble, B. W., Patel, S., Woodgett, J. R., & Snider, W. D.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- McMaster University (CA)
- Mount Sinai Hospital (CA)
- Corresponding author
- Snider, William D
- Venue
- Nature Neuroscience
- Published
- 2009-10-04
- Volume
- 12
- Issue
- 11
- Pages
- 1390-1397
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5328673
- OpenAlex
- W1993145412
- Cited by
- 399
- References
- 39
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 11 · 2023: 15 · 2022: 17 · 2021: 16 · 2020: 32 · 2019: 21 · 2018: 21 · 2017: 33 · 2016: 23 · 2015: 28 · 2014: 36 · 2013: 33 · 2012: 28
- FWCI
- 10.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (NS045892)
- Canadian Institutes of Health Research (12858, 74711, MOP74711)
- National Institute of Neurological Disorders and Stroke (P30NS045892, NS050968, NS045892, R01NS050968)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- glycogen synthase kinase-3, GSK3β, neural progenitor proliferation, conditional knockout, β-catenin signaling, Sonic hedgehog signaling, Notch signaling, FGF signaling, brain development, intermediate neural progenitors, postmitotic neurons
- MeSH terms
- Animals, Bromodeoxyuridine, Cell Differentiation, Cells, Cultured, Embryo, Mammalian, Homeostasis, Humans, Intermediate Filament Proteins, Mutation, Nerve Tissue Proteins, Neurons, Stem Cells, Transcription Factors, Transfection, Signal Transduction, Mice, Knockout, Gene Expression Regulation, Developmental, Neocortex, Glycogen Synthase Kinase 3, Cell Proliferation, Mice, Nestin
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