title: MicroRNA-15b promotes neurogenesis and inhibits neural progenitor proliferation by directly repressing TET3 during early neocortical development.
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.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xuepei
authors.initials: X
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China jwjiao@ioz.ac.cn.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Jiao
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D049308:Dioxygenases; D005260:Female; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D019579:Neocortex / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C551915:Tet3 protein, mouse
keywords: TET3; miR‐15b; neocortical development; neural progenitors; proliferation