CDK7 and miR-210 Co-regulate Cell-Cycle Progression of Neural Progenitors in the Developing Neocortex

Autor: Haijun Zhang, Yanzhen Nie, Aisha Iman Abdullah, Wei Tang, Tao Sun
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Stem Cell Reports
Stem Cell Reports, Vol 7, Iss 1, Pp 69-79 (2016)
ISSN: 2213-6711
Popis: Summary The molecular mechanisms regulating neural progenitor (NP) proliferation are fundamental in establishing the cytoarchitecture of the mammalian neocortex. The rate of cell-cycle progression and a fine-tuned balance between cell-cycle re-entry and exit determine the numbers of both NPs and neurons as well as postmitotic neuronal laminar distribution in the cortical wall. Here, we demonstrate that the microRNA (miRNA) miR-210 is required for normal mouse NP cell-cycle progression. Overexpression of miR-210 promotes premature cell-cycle exit and terminal differentiation in NPs, resulting in an increase in early-born postmitotic neurons. Conversely, miR-210 knockdown promotes an increase in the radial glial cell population and delayed differentiation, resulting in an increase in late-born postmitotic neurons. Moreover, the cyclin-dependent kinase CDK7 is regulated by miR-210 and is necessary for normal NP cell-cycle progression. Our findings demonstrate that miRNAs are essential for normal NP proliferation and cell-cycle progress during neocortical development.
Graphical Abstract
Highlights • miR-210 level is essential for cell-cycle progression in cortical neural progenitors • Cdk7 and miR-210 control neural progenitor proliferation • miR-210 promotes premature cell-cycle exit and differentiation in neural progenitors • miR-210 expression induces a deep-layer neuronal fate in the neocortex
In this article, Sun, Tang, and colleagues demonstrate that miR-210 and its target gene cyclin-dependent kinase Cdk7 co-regulate neural progenitor proliferation in the developing mouse neocortex. They further demonstrate that miR-210 expression induces premature cell-cycle exit and differentiation in neural progenitors, thereby promoting a deep cortical layer fate in postmitotic neurons.
Databáze: OpenAIRE