Micro RNA ‐15b promotes neurogenesis and inhibits neural progenitor proliferation by directly repressing TET 3 during early neocortical development

Micro RNA s (mi RNA s) 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 mi RNA 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 TET 3, which plays crucial roles during embryonic development by enhancing DNA demethylation. TET 3 promotes cyclin D1 expression, and miR‐15b reduces TET 3 expression and 5hmC levels. Notably, TET 3 expression rescues miR‐15b‐induced impaired NPC proliferation and increased cell‐cycle exit in vivo . Our results not only reveal a link between mi RNA s, TET , and DNA demethylation but also demonstrate critical roles for miR‐15b and TET 3 in maintaining the NPC pool during early neocortical development.