title: The Silencing Effect of microRNA miR-17 on p21 Maintains the Neural Progenitor Pool in the Developing Cerebral Cortex.
abstract: Expansion of the neural progenitor pool in the developing cerebral cortex is crucial for controlling brain size, since proliferation defects have been associated with the pathogenesis of microcephaly in humans. Cell cycle regulators play important roles in proliferation of neural progenitors. Here, we show that the cyclin-dependent kinase inhibitor p21 (also called Cdkn1a and Cip1) negatively regulates proliferation of radial glial cells (RGCs) and intermediate progenitors (IPs) in the embryonic mouse cortex. MicroRNA-17 (miR-17) displays reciprocal expressions with p21 in the developing cortex. Opposite to p21, miR-17 promotes expansion of RGCs and IPs, as demonstrated by overexpressing miR-17 precursors and miR-17 sponges that can knock down the endogenous miR-17. Moreover, p21 is a putative target normally silenced by miR-17. Co-expression of miR-17 with p21 is sufficient to rescue the negative regulation of p21 on progenitor proliferation. Our results indicate a mechanism of controlling the neural progenitor pool, which is to suppress p21 by miR-17 in the developing cortex.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University , Changsha , China ; Department of Cell and Developmental Biology, Weill Medical College of Cornell University , New York, NY , USA.
authors.forename: Yase
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University , New York, NY , USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Bian
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University , New York, NY , USA.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University , Changsha , China.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University , New York, NY , USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
keywords: cerebral cortex; miR-17; miRNAs; p21; proliferation
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