title: Loss of motoneuron-specific microRNA-218 causes systemic neuromuscular failure.
abstract: 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 TARGET(218), defines a neuronal gene network that is selectively tuned down in motoneurons to prevent neuromuscular failure and neurodegeneration.
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Medical Scientist Training Program, University of California, San Diego (UCSD), 9500 Gilman Drive, La Jolla, CA 92037, USA. Biomedical Sciences Graduate Program, UCSD, 9500 Gilman Drive, La Jolla, CA 92037, USA.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Amin
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Ge
authors.initials: G
authors.lastname: Bai
authors.affiliation: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Klug
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Dario
authors.initials: D
authors.lastname: Bonanomi
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Pankratz
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Medical Scientist Training Program, University of California, San Diego (UCSD), 9500 Gilman Drive, La Jolla, CA 92037, USA. Neurosciences Graduate Program, UCSD, 9500 Gilman Drive, La Jolla, CA 92037, USA.
authors.forename: Wesley D
authors.initials: WD
authors.lastname: Gifford
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hinckley
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Biological Sciences Graduate Program, UCSD, 9500 Gilman Drive, La Jolla, CA 92037, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sternfeld
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Driscoll
authors.affiliation: Peptide Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Bertha
authors.initials: B
authors.lastname: Dominguez
authors.affiliation: Peptide Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Kuo-Fen
authors.initials: KF
authors.lastname: Lee
authors.affiliation: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. pfaff@salk.edu.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Pfaff
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D016472:Motor Neuron Disease / Q000235:genetics* / Q000503:physiopathology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology
chemical_list: C547684:MIRN218 microRNA, mouse; D035683:MicroRNAs