Astrocytes Negatively Regulate Neurogenesis Through the Jagged1‐Mediated Notch Pathway
Abstract
Adult neurogenesis is regulated by a number of cellular players within the neurogenic niche. Astrocytes participate actively in brain development, regulation of the mature central nervous system (CNS), and brain plasticity. They are important regulators of the local environment in adult neurogenic niches through the secretion of diffusible morphogenic factors, such as Wnts. Astrocytes control the neurogenic niche also through membrane-associated factors, however, the identity of these factors and the mechanisms involved are largely unknown. In this study, we sought to determine the mechanisms underlying our earlier finding of increased neuronal differentiation of neural progenitor cells when cocultured with astrocytes lacking glial fibrillary acidic protein (GFAP) and vimentin (GFAP(-/-) Vim(-/-) ). We used primary astrocyte and neurosphere cocultures to demonstrate that astrocytes inhibit neuronal differentiation through a cell-cell contact. GFAP(-/-) Vim(-/-) astrocytes showed reduced endocytosis of Notch ligand Jagged1, reduced Notch signaling, and increased neuronal differentiation of neurosphere cultures. This effect of GFAP(-/-) Vim(-/-) astrocytes was abrogated in the presence of immobilized Jagged1 in a manner dependent on the activity of γ-secretase. Finally, we used GFAP(-/-) Vim(-/-) mice to show that in the absence of GFAP and vimentin, hippocampal neurogenesis under basal conditions as well as after injury is increased. We conclude that astrocytes negatively regu…
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Gfap−/−Vim−/− mice exhibit better posttraumatic regeneration of neuronal synapses and axons, increased baseline and posttraumatic neurogenesis, and improved functional recovery after spinal cord trauma.
“Interestingly, Gfap−/−Vim−/− mice exhibit better posttraumatic regeneration of neuronal synapses (23) and axons (34), increased baseline and posttraumatic neurogenesis (35), and improved functional recovery after spinal cord trauma (36).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [35]
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- Authors
- Wilhelmsson, U., Faiz, M., de Pablo, Y., Sjöqvist, M., Andersson, D., Widestrand, Å., Potokar, M., Stenovec, M., Smith, P. L. P., Shinjyo, N., Pekny, T., Zorec, R., Ståhlberg, A., Pekna, M., Sahlgren, C., & Pekny, M.
- Affiliations
- University of Gothenburg (SE)
- Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Åbo Akademi University (FI)
- University of Ljubljana (SI)
- Ikerbasque (ES)
- Corresponding author
- Pekny, Milos
- ORCID
- Venue
- STEM CELLS
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-09-20
- Volume
- 30
- Issue
- 10
- Pages
- 2320-2329
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2153591334
- Cited by
- 145
- References
- 6
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 5 · 2021: 14 · 2020: 14 · 2019: 11 · 2018: 10 · 2017: 19 · 2016: 10 · 2015: 14 · 2014: 13 · 2013: 13 · 2012: 3
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Stem Cells (publishedVersion)
- PubMed (publishedVersion)
- TU/e Research Portal (submittedVersion)
- Åbo Akademi University Research Portal (submittedVersion)
- Funders
- Judith Jane Mason and Harold Stannett Williams Memorial Foundation
- European Commission (279017, 237956)
- Svenska Sällskapet för Medicinsk Forskning
- Medical Research Council
- 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 › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- astrocytes, adult neurogenesis, Notch signaling, Jagged1, neurogenic niche, glial fibrillary acidic protein, vimentin, intermediate filaments, neuronal differentiation, neural progenitor cells, neurospheres, gamma-secretase, cell-cell contact, hippocampal neurogenesis, brain injury, astrocyte-neuron interaction
- MeSH terms
- Serrate-Jagged Proteins, Jagged-1 Protein, Animals, Astrocytes, Calcium-Binding Proteins, Cell Communication, Cell Differentiation, Endocytosis, Glial Fibrillary Acidic Protein, Male, Membrane Proteins, Nerve Tissue Proteins, Stem Cells, Vimentin, Signal Transduction, Mice, Knockout, Gene Expression Regulation, Developmental, Coculture Techniques, Intercellular Signaling Peptides and Proteins, Wnt Proteins, Mice, Receptors, Notch, Amyloid Precursor Protein Secretases, Neurogenesis, Primary Cell Culture
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