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

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.