Growth of the Developing Cerebral Cortex Is Controlled by MicroRNA-7 through the p53 Pathway
Open accessAbstract
Proper growth of the mammalian cerebral cortex is crucial for normal brain functions and is controlled by precise gene-expression regulation. Here, we show that microRNA-7 (miR-7) is highly expressed in cortical neural progenitors and describe miR-7 sponge transgenic mice in which miR-7-silencing activity is specifically knocked down in the embryonic cortex. Blocking miR-7 function causes microcephaly-like brain defects due to reduced intermediate progenitor (IP) production and apoptosis. Upregulation of miR-7 target genes, including those implicated in the p53 pathway, such as Ak1 and Cdkn1a (p21), is responsible for abnormalities in neural progenitors. Furthermore, ectopic expression of Ak1 or p21 and specific blockade of miR-7 binding sites in target genes using protectors in vivo induce similarly reduced IP production. Using conditional miRNA sponge transgenic approaches, we uncovered an unexpected role for miR-7 in cortical growth through its interactions with genes in the p53 pathway.
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miRNAs selectively regulate genes within the same pathway.
“Recent studies demonstrated that miRNAs selectively regulate genes within the same pathway [97, 131-133].”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [133]
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- Authors
- Pollock, A., Bian, S., Zhang, C., Chen, Z., & Sun, T.
- Affiliations
- Cornell University (US)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Sun, Tao
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 7
- Issue
- 4
- Pages
- 1184-1196
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4067415
- OpenAlex
- W2000600282
- Cited by
- 88
- References
- 46
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 11 · 2023: 3 · 2022: 3 · 2021: 10 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 9 · 2016: 11 · 2015: 7 · 2014: 2
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-07-24)
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (UL1TR000457)
- National Institute of Mental Health (R01MH083680)
- National Center for Research Resources (UL1RR024996)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- microRNA-7, cortical development, p53 pathway, intermediate progenitor cells, microcephaly, apoptosis, AK1, p21, gene expression regulation, embryonic brain
- MeSH terms
- Animals, Cerebral Cortex, Gene Expression Regulation, Mice, Transgenic, Tumor Suppressor Protein p53, MicroRNAs, Cell Line, Tumor, Mice
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