microRNA-34a regulates neurite outgrowth, spinal morphology, and function

被引:158
作者
Agostini, Massimiliano [1 ]
Tucci, Paola [1 ,2 ]
Steinert, Joern R. [1 ]
Shalom-Feuerstein, Ruby [3 ,4 ]
Rouleau, Matthieu [3 ,4 ]
Aberdam, Daniel [3 ,4 ]
Forsythe, Ian D. [1 ]
Young, Kenneth W. [1 ]
Ventura, Andrea [5 ]
Concepcion, Carla P. [5 ]
Han, Yoon-Chi [5 ]
Candi, Eleonora [2 ]
Knight, Richard A. [1 ]
Mak, Tak W. [6 ]
Melino, Gerry [1 ,2 ]
机构
[1] Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England
[2] Univ Roma Tor Vergata, Biochem Lab, Ist Dermopat Immacolata, Ist Ricovero & Cura Carattere Sci, I-00133 Rome, Italy
[3] Univ Nice Sophia Antipolis, INSERM, U898, F-06107 Nice, France
[4] Technion Israel Inst Technol, INSERTECH, Rappaport Family Inst Res Med Sci, IL-31096 Haifa, Israel
[5] Mem Sloan Kettering Canc Ctr, Canc Genet & Biol Program, New York, NY 10065 USA
[6] Princess Margaret Hosp, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada
基金
英国医学研究理事会;
关键词
cell death; synaptogenesis; neuronal differentiation; hippocampus; EMBRYONIC STEM-CELLS; GENE-EXPRESSION; P53; DIFFERENTIATION; APOPTOSIS; MIR-34A; P73; ACTIVATION; VARIANTS; NANOG;
D O I
10.1073/pnas.1112063108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The p53 family member TAp73 is a transcription factor that plays a key role in many biological processes, including neuronal development. In particular, we have shown that p73 drives the expression of miR-34a, but not miR-34b and c, in mouse cortical neurons. miR-34a in turn modulates the expression of synaptic targets including synaptotagmin-1 and syntaxin-1A. Here we show that this axis is retained in mouse ES cells committed to differentiate toward a neurological phenotype. Moreover, overexpression of miR-34a alters hippocampal spinal morphology, and results in electrophysiological changes consistent with a reduction in spinal function. Therefore, the TAp73/miR-34a axis has functional relevance in primary neurons. These data reinforce a role for miR-34a in neuronal development.
引用
收藏
页码:21099 / 21104
页数:6
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