title: Timing specific requirement of microRNA function is essential for embryonic and postnatal hippocampal development.
abstract: The adult hippocampus consists of the dentate gyrus (DG) and the CA1, CA2 and CA3 regions and is essential for learning and memory functions. During embryonic development, hippocampal neurons are derived from hippocampal neuroepithelial cells and dentate granular progenitors. The molecular mechanisms that control hippocampal progenitor proliferation and differentiation are not well understood. Here we show that noncoding microRNAs (miRNAs) are essential for early hippocampal development in mice. Conditionally ablating the RNAase III enzyme Dicer at different embryonic time points utilizing three Cre mouse lines causes abnormal hippocampal morphology and affects the number of hippocampal progenitors due to altered proliferation and increased apoptosis. Lack of miRNAs at earlier stages causes early differentiation of hippocampal neurons, in particular in the CA1 and DG regions. Lack of miRNAs at a later stage specifically affects neuronal production in the CA3 region. Our results reveal a timing requirement of miRNAs for the formation of specific hippocampal regions, with the CA1 and DG developmentally hindered by an early loss of miRNAs and the CA3 region to a late loss of miRNAs. Collectively, our studies indicate the importance of the Dicer-mediated miRNA pathway in hippocampal development and functions.
authors: Department of Cell and Developmental Biology, Weill Medical College, Cornell University, New York, New York, United States of America.
authors: Qingsong
authors: Q
authors: Li
authors: Shan
authors: S
authors: Bian
authors: Janet
authors: J
authors: Hong
authors: Yoko
authors: Y
authors: Kawase-Koga
authors: Edwin
authors: E
authors: Zhu
authors: Yongri
authors: Y
authors: Zheng
authors: Lizhuang
authors: L
authors: Yang
authors: Tao
authors: T
authors: Sun
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D047108:Embryonic Development / Q000235:genetics*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D043244:Ribonuclease III