Abstract
MicroRNAs (miRNAs) are important regulators of mouse brain development. However, their precise roles in this context remain to be elucidated. Through screening of expression profiles from a miRNA microarray and experimental analysis, we show here that miR-15b controls several aspects of cortical neurogenesis. miR-15b inhibits cortical neural progenitor cell (NPC) proliferation and promotes cell-cycle exit and neuronal differentiation. Additionally, miR-15b expression decreases the number of apical progenitors and increases basal progenitors in the VZ/SVZ. We also show that miR-15b binds to the 3' UTR of TET3, which plays crucial roles during embryonic development by enhancing DNA demethylation. TET3 promotes cyclin D1 expression, and miR-15b reduces TET3 expression and 5hmC levels. Notably, TET3 expression rescues miR-15b-induced impaired NPC proliferation and increased cell-cycle exit in vivo. Our results not only reveal a link between miRNAs, TET, and DNA demethylation but also demonstrate critical roles for miR-15b and TET3 in maintaining the NPC pool during early neocortical development.
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