Persistent Cyfip1 Expression Is Required to Maintain the Adult Subventricular Zone Neurogenic Niche
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Abstract
Neural stem cells (NSCs) persist throughout life in the subventricular zone (SVZ) neurogenic niche of the lateral ventricles as Type B1 cells in adult mice. Maintaining this population of NSCs depends on the balance between quiescence and self-renewing or self-depleting cell divisions. Interactions between B1 cells and the surrounding niche are important in regulating this balance, but the mechanisms governing these processes have not been fully elucidated. The cytoplasmic FMRP-interacting protein (Cyfip1) regulates apical-basal polarity in the embryonic brain. Loss of Cyfip1 during embryonic development in mice disrupts the embryonic niche and affects cortical neurogenesis. However, a direct role for Cyfip1 in the regulation of adult NSCs has not been established. Here, we demonstrate that Cyfip1 expression is preferentially localized to B1 cells in the adult mouse SVZ. Loss of Cyfip1 in the embryonic mouse brain results in altered adult SVZ architecture and expansion of the adult B1 cell population at the ventricular surface. Furthermore, acute deletion of Cyfip1 in adult NSCs results in a rapid change in adherens junction proteins as well as increased proliferation and number of B1 cells at the ventricular surface. Together, these data indicate that Cyfip1 plays a critical role in the formation and maintenance of the adult SVZ niche; furthermore, deletion of Cyfip1 unleashes the capacity of adult B1 cells for symmetric renewal to increase the adult NSC pool. SIGNIFICANCE STATEMENT Neural stem cells (NSCs) persist in the subventricular zone of the lateral ventricles in adult mammals, and the size of this population is determined by the balance between quiescence and self-depleting or renewing cell division. The mechanisms regulating these processes are not fully understood. This study establishes that the cytoplasmic FMRP interacting protein 1 (Cyfip1) regulates NSC fate decisions in the adult subventricular zone and adult NSCs that are quiescent or typically undergo self-depleting divisions retain the ability to self-renew. These results contribute to our understanding of how adult NSCs are regulated throughout life and has potential implications for human brain disorders.
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CYFIP1 is required for neural stem cell activity in the subventricular zone and maintenance of the neurogenic niche of the lateral ventricles and thereby cortical neurogenesis in adult mice.
“CYFIP1 is required for neural stem cell activity in the subventricular zone and maintenance of the neurogenic niche of the lateral ventricles and thereby cortical neurogenesis in adult mice75 (Fig. 4a).”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [75]
The Abstract and Discussion (page numbers unavailable) support a role for Cyfip1 in adult mouse SVZ stem-cell behavior and maintenance of the lateral-ventricle neurogenic niche. They do not support the claimed consequence for cortical neurogenesis in adult mice: the Abstract places the cortical-neurogenesis effect during embryonic development, and the Discussion reports no immediate increase in neurogenesis after acute adult Cyfip1 loss. (LLM, conf=0.91)
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Cites
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“Germline deletion of Cyfip1 is embryonic lethal (Pathania et al., 2014).”
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The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
- Authors
- Habela, C. W., Yoon, K.-J., Kim, N.-S., Taga, A., Bell, K., Bergles, D. E., Maragakis, N. J., Ming, G.-L., & Song, H.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Habela, Christa Whelan
- Song, Hongjun
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2020-01-27
- Volume
- 40
- Issue
- 10
- Pages
- 2015-2024
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC7055134
- OpenAlex
- W3004105150
- Cited by
- 16
- References
- 13
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 2 · 2021: 1 · 2020: 2 · 2019: 1
- FWCI
- 0.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH1810174)
- Simons Foundation Autism Research Initiative
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R25NS065729, R35NS097370, R37NS047344, K12NS098482)
- 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
- CYFIP1, subventricular zone, neural stem cells, neurogenic niche, self-renewal, symmetric cell division, quiescent cells, adherens junctions, apical-basal polarity, FMRP, adult neurogenesis
- MeSH terms
- Aging, Animals, Mice, Inbred C57BL, Mice, Transgenic, Lateral Ventricles, Adaptor Proteins, Signal Transducing, Mice, Adult Stem Cells, Stem Cell Niche, Neurogenesis, Neural Stem Cells
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