Cited by 88Neurogenesis and neuroplasticity mechanismsMicroRNA in disease regulationDevelopmental Biology and Gene Regulation

Growth of the Developing Cerebral Cortex Is Controlled by MicroRNA-7 through the p53 Pathway

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Pollock, Andrew, Bian, Shan, Zhang, Chao, Chen, Zhengming, Sun, Tao·2014·Cell Reports

Abstract

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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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)
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
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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