Two miRNA clusters, <i>miR-34b/c</i> and <i>miR-449</i> , are essential for normal brain development, motile ciliogenesis, and spermatogenesis

Jingwen Wu(University of Nevada, Reno), Jianqiang Bao(University of Nevada, Reno), Min Kyung Kim(University of Nevada, Reno), Shuiqiao Yuan(University of Nevada, Reno), Chong Tang(University of Nevada, Reno), Huili Zheng(University of Nevada, Reno), Grant S. Mastick(University of Nevada, Reno), Chen Xu(Shanghai Jiao Tong University), Wei Yan(University of Nevada, Reno)
Proceedings of the National Academy of Sciences
June 30, 2014
10.1073/pnas.1407777111
Cited by 266Open Access
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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.

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