Loss of motoneuron-specific microRNA-218 causes systemic neuromuscular failure

被引：133

作者：

Amin, Neal D. ^{[1
,2
,3
,4
]}

Bai, Ge ^{[1
,2
]}

Klug, Jason R. ^{[5
]}

Bonanomi, Dario ^{[1
,2
]}

Pankratz, Matthew T. ^{[1
,2
]}

Gifford, Wesley D. ^{[1
,2
,3
,6
]}

Hinckley, Christopher A. ^{[1
,2
]}

Sternfeld, Matthew J. ^{[1
,2
,7
]}

Driscoll, Shawn P. ^{[1
,2
]}

Dominguez, Bertha ^{[8
]}

Lee, Kuo-Fen ^{[8
]}

Jin, Xin ^{[5
]}

Pfaff, Samuel L. ^{[1
,2
]}

机构：

[1] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA

[2] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA

[3] Univ Calif San Diego, Med Scientist Training Program, La Jolla, CA 92037 USA

[4] UCSD, Biomed Sci Grad Program, La Jolla, CA 92037 USA

[5] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA

[6] UCSD, Neurosci Grad Program, La Jolla, CA 92037 USA

[7] UCSD, Biol Sci Grad Program, La Jolla, CA 92037 USA

[8] Salk Inst Biol Studies, Peptide Biol Lab, La Jolla, CA 92037 USA

来源：

SCIENCE | 2015年 / 350卷 / 6267期

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURONS; SPINAL-CORD; IN-VIVO; HYPEREXCITABILITY; BIOGENESIS; MIR-218; BINDING; DROSHA; FATE;

D O I：

10.1126/science.aad2509

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Dysfunction of microRNA (miRNA) metabolism is thought to underlie diseases affecting motoneurons. One miRNA, miR-218, is abundantly and selectively expressed by developing and mature motoneurons. Here we show that mutant mice lacking miR-218 die neonatally and exhibit neuromuscular junction defects, motoneuron hyperexcitability, and progressive motoneuron cell loss, all of which are hallmarks of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Gene profiling reveals that miR-218 modestly represses a cohort of hundreds of genes that are neuronally enriched but are not specific to a single neuron subpopulation. Thus, the set of messenger RNAs targeted by miR-218, designated TARGET218, defines a neuronal gene network that is selectively tuned down in motoneurons to prevent neuromuscular failure and neurodegeneration.

引用

页码：1525 / 1529

页数：5

共 28 条

[11]

Activity of Hb9 Interneurons during Fictive Locomotion in Mouse Spinal Cord [J].

Kwan, Alex C. ;

Dietz, Shelby B. ;

Webb, Watt W. ;

Harris-Warrick, Ronald M. .

JOURNAL OF NEUROSCIENCE, 2009, 29 (37) :11601-11613

[12]

Spinal muscular atrophy patient-derived motor neurons exhibit hyperexcitability [J].

Liu, Huisheng ;

Lu, Jianfeng ;

Chen, Hong ;

Du, Zhongwei ;

Li, Xue-Jun ;

Zhang, Su-Chun .

SCIENTIFIC REPORTS, 2015, 5

[13]

Conserved roles for slit and robo proteins in midline commissural axon guidance [J].

Long, H ;

Sabatier, C ;

Ma, L ;

Plump, A ;

Yuan, WL ;

Ornitz, DM ;

Tamada, A ;

Murakami, F ;

Goodman, CS ;

Tessier-Lavigne, M .

NEURON, 2004, 42 (02) :213-223

[14]

MiR-218 Mediates tumorigenesis and metastasis: Perspectives and implications [J].

Lu, Ying-fei ;

Zhang, Li ;

Waye, Mary Miu Yee ;

Fu, Wei-ming ;

Zhang, Jin-fang .

EXPERIMENTAL CELL RESEARCH, 2015, 334 (01) :173-182

[15]

Dual branch-promoting and branch-repelling actions of slit/robo signaling on peripheral and central branches of developing sensory axons [J].

Ma, Le ;

Tessier-Lavigne, Marc .

JOURNAL OF NEUROSCIENCE, 2007, 27 (25) :6843-6851

[16]

The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative Pre-mRNA splicing [J].

Makeyev, Eugene V. ;

Zhang, Jiangwen ;

Carrasco, Monica A. ;

Maniatis, Tom .

MOLECULAR CELL, 2007, 27 (03) :435-448

[17]

Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity [J].

Mazzoni, Esteban O. ;

Mahony, Shaun ;

Closser, Michael ;

Morrison, Carolyn A. ;

Nedelec, Stephane ;

Williams, Damian J. ;

An, Disi ;

Gifford, David K. ;

Wichterle, Hynek .

NATURE NEUROSCIENCE, 2013, 16 (09) :1219-U86

[18]

DeCoN: Genome-wide Analysis of In Vivo Transcriptional Dynamics during Pyramidal Neuron Fate Selection in Neocortex [J].

Molyneaux, Bradley J. ;

Goff, Loyal A. ;

Brettler, Andrea C. ;

Chen, Hsu-Hsin ;

Brown, Juliana R. ;

Hrvatin, Sinisa ;

Rinn, John L. ;

Arlotta, Paola .

NEURON, 2015, 85 (02) :275-288

[19]

FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment [J].

Morlando, Mariangela ;

Modigliani, Stefano Dini ;

Torrelli, Giulia ;

Rosa, Alessandro ;

Di Carlo, Valerio ;

Caffarelli, Elisa ;

Bozzoni, Irene .

EMBO JOURNAL, 2012, 31 (24) :4502-4510

[20]

Amyotrophic lateral sclerosis: mechanisms and therapeutics in the epigenomic era [J].

Paez-Colasante, Ximena ;

Figueroa-Romero, Claudia ;

Sakowski, Stacey A. ;

Goutman, Stephen A. ;

Feldman, Eva L. .

NATURE REVIEWS NEUROLOGY, 2015, 11 (05) :266-279

← 1 2 3 →