期刊
CELL
卷 152, 期 1-2, 页码 262-275出版社
CELL PRESS
DOI: 10.1016/j.cell.2012.11.052
关键词
-
资金
- Simons Foundation
- US National Institute of Mental Health [MH67068, MH077235, MH97879]
- March of Dimes Foundation
- McKnight Endowment Fund for Neuroscience
- National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award
- NARSAD Suzanne and John Golden Young Investigator Award
22q11.2 microdeletions result in specific cognitive deficits and schizophrenia. Analysis of Df(16)A(+/-) mice, which model this microdeletion, revealed abnormalities in the formation of neuronal dendrites and spines, as well as altered brain microRNAs. Here, we show a drastic reduction of miR-185, which resides within the 22q11.2 locus, to levels more than expected by a hemizygous deletion, and we demonstrate that this reduction alters dendritic and spine development. miR-185 represses, through an evolutionarily conserved target site, a previously unknown inhibitor of these processes that resides in the Golgi apparatus and shows higher prenatal brain expression. Sustained derepression of this inhibitor after birth represents the most robust transcriptional disturbance in the brains of Df(16)A(+/-) mice and results in structural alterations in the hippocampus. Reduction of miR-185 also has milder age- and region-specific effects on the expression of some Golgi-related genes. Our findings illuminate the contribution of microRNAs in psychiatric disorders and cognitive dysfunction.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据