title: Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis.
abstract: Ablation of a single miRNA gene rarely leads to a discernable developmental phenotype in mice, in some cases because of compensatory effects by other functionally related miRNAs. Here, we report that simultaneous inactivation of two functionally related miRNA clusters (miR-34b/c and miR-449) encoding five miRNAs (miR-34b, miR-34c, miR-449a, miR-449b, and miR-449c) led to sexually dimorphic, partial perinatal lethality, growth retardation, and infertility. These developmental defects correlated with the dysregulation of ∼ 240 target genes, which are mainly involved in three major cellular functions, including cell-fate control, brain development and microtubule dynamics. Our data demonstrate an essential role of a miRNA family in brain development, motile ciliogenesis, and spermatogenesis.
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557;Department of Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; and.
authors: Jingwen
authors: J
authors: Wu
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557;
authors: Jianqiang
authors: J
authors: Bao
authors: Department of Biology, University of Nevada, Reno, NV 89557.
authors: Minkyung
authors: M
authors: Kim
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557;
authors: Shuiqiao
authors: S
authors: Yuan
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557;
authors: Chong
authors: C
authors: Tang
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557;
authors: Huili
authors: H
authors: Zheng
authors: Department of Biology, University of Nevada, Reno, NV 89557.
authors: Grant S
authors: GS
authors: Mastick
authors: Department of Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; and chenx@shsmu.edu.cn wyan@medicine.nevada.edu.
authors: Chen
authors: C
authors: Xu
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557; chenx@shsmu.edu.cn wyan@medicine.nevada.edu.
authors: Wei
authors: W
authors: Yan
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology*
chemical_list: C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; C538721:Mirn449 microRNA, mouse
keywords: airway obstruction; egg transport; forebrain; oviduct