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

被引：160

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

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 52期

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

页码：21099 / 21104

页数：6

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