MicroRNA Cluster miR-17-92 Regulates Neural Stem Cell Expansion and Transition to Intermediate Progenitors in the Developing Mouse Neocortex

• The miR-17-92 cluster is expressed in the cortical ventricular zone
• Knockout of miR-17-92 suppresses expansion of cortical neural stem cells
• Transition of intermediate progenitors is controlled by miR-17-92
• miR-17-92 regulates neural stem cell development by targeting Pten and Tbr2

SummaryDuring development of the embryonic neocortex, tightly regulated expansion of neural stem cells (NSCs) and their transition to intermediate progenitors (IPs) are critical for normal cortical formation and function. Molecular mechanisms that regulate NSC expansion and transition remain unclear. Here, we demonstrate that the microRNA (miRNA) miR-17-92 cluster is required for maintaining proper populations of cortical radial glial cells (RGCs) and IPs through repression of Pten and Tbr2 protein. Knockout of miR-17-92 and its paralogs specifically in the developing neocortex restricts NSC proliferation, suppresses RGC expansion, and promotes transition of RGCs to IPs. Moreover, Pten and Tbr2 protectors specifically block silencing activities of endogenous miR-17-92 and control proper numbers of RGCs and IPs in vivo. Our results demonstrate a critical role for miRNAs in promoting NSC proliferation and modulating the cell-fate decision of generating distinct neural progenitors in the developing neocortex.

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