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

•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

SummaryThe 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.

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