title: Growth of the developing cerebral cortex is controlled by microRNA-7 through the p53 pathway.
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.
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, Box 60, New York, NY 10065, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pollock
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, Box 60, New York, NY 10065, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Bian
authors.affiliation: Department of Medicine and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Public Health, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, Box 60, New York, NY 10065, USA; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: tas2009@med.cornell.edu.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: C549243:MIRN7 microRNA, mouse; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53