The Wnt/β-catenin pathway directs neuronal differentiation of cortical neural precursor cells
Open accessAbstract
Neural precursor cells (NPCs) have the ability to self-renew and to give rise to neuronal and glial lineages. The fate decision of NPCs between proliferation and differentiation determines the number of differentiated cells and the size of each region of the brain. However, the signals that regulate the timing of neuronal differentiation remain unclear. Here, we show that Wnt signaling inhibits the self-renewal capacity of mouse cortical NPCs,and instructively promotes their neuronal differentiation. Overexpression of Wnt7a or of a stabilized form of β-catenin in mouse cortical NPC cultures induced neuronal differentiation even in the presence of Fgf2, a self-renewal-promoting factor in this system. Moreover, blockade of Wnt signaling led to inhibition of neuronal differentiation of cortical NPCs in vitro and in the developing mouse neocortex. Furthermore, theβ-catenin/TCF complex appears to directly regulate the promoter of neurogenin 1, a gene implicated in cortical neuronal differentiation. Importantly, stabilized β-catenin did not induce neuronal differentiation of cortical NPCs at earlier developmental stages, consistent with previous reports indicating self-renewal-promoting functions of Wnts in early NPCs. These findings may reveal broader and stage-specific physiological roles of Wnt signaling during neural development.
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Wnt signaling controls NPCs proliferation and differentiation in a temporal and context-dependent fashion during brain development.
“It is known that Wnt signaling controls NPCs proliferation and differentiation in a temporal and context-dependent fashion during brain development.”
From Altered proliferation and networks in neural cells derived from idiopathic autistic individuals (2017) · cites this paper as [55]
Early in neurogenesis, Wnt stimulation results in NPC proliferation, whereas later in development Wnts induce neuronal differentiation by promoting terminal neurogenesis.
“Early in neurogenesis, Wnt stimulation results in NPC proliferation, whereas later in development Wnts induce neuronal differentiation by promoting terminal neurogenesis 54-56.”
From Altered proliferation and networks in neural cells derived from idiopathic autistic individuals (2017) · cites this paper as [55]
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- Authors
- Hirabayashi, Y., Itoh, Y., Tabata, H., Nakajima, K., Akiyama, T., Masuyama, N., & Gotoh, Y.
- Affiliations
- Institute for Quantitative Biosciences, The University of Tokyo (JP)
- Jikei University School of Medicine (JP)
- National Institute for Physiological Sciences (JP)
- Corresponding author
- Gotoh, Yukiko
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2004-06-15
- Volume
- 131
- Issue
- 12
- Pages
- 2791-2801
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W1995030818
- Cited by
- 600
- References
- 62
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 15 · 2023: 21 · 2022: 16 · 2021: 20 · 2020: 27 · 2019: 26 · 2018: 24 · 2017: 28 · 2016: 27 · 2015: 23 · 2014: 45 · 2013: 37 · 2012: 38
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- 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
- Wnt/β-catenin signaling, neuronal differentiation, neural stem cell self-renewal, Wnt7a, neurogenin1, TCF transcription factors, FGF2, neocortex development, neural development
- MeSH terms
- Animals, Base Sequence, Cell Differentiation, Cells, Cultured, Cerebral Cortex, Cloning, Molecular, Cytoskeletal Proteins, Extremities, Neuroglia, Neurons, Promoter Regions, Genetic, Proto-Oncogene Proteins, Recombinant Proteins, Stem Cells, Signal Transduction, Trans-Activators, DNA Primers, Gene Expression Regulation, Developmental, Reverse Transcriptase Polymerase Chain Reaction, Wnt Proteins, beta Catenin, Mice
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