The Role of Muscle microRNAs in Repairing the Neuromuscular Junction
microRNAs have been implicated in mediating key aspects of skeletal muscle development and responses to diseases and injury. Recently, we demonstrated that a synaptically enriched microRNA, miR-206, functions to promote maintenance and repair of the neuromuscular junction (NMJ); in mutant mice lacki...
| Main Authors: | , , , |
|---|---|
| 其他作者: | |
| 格式: | 文件 |
| 语言: | en_US |
| 出版: |
Public Library of Science
2014
|
| 在线阅读: | http://hdl.handle.net/1721.1/86187 https://orcid.org/0000-0002-8021-277X |
| _version_ | 1826211348997996544 |
|---|---|
| author | Valdez, Gregorio Heyer, Mary P. Feng, Guoping Sanes, Joshua R. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Valdez, Gregorio Heyer, Mary P. Feng, Guoping Sanes, Joshua R. |
| author_sort | Valdez, Gregorio |
| collection | MIT |
| description | microRNAs have been implicated in mediating key aspects of skeletal muscle development and responses to diseases and injury. Recently, we demonstrated that a synaptically enriched microRNA, miR-206, functions to promote maintenance and repair of the neuromuscular junction (NMJ); in mutant mice lacking miR-206, reinnervation is impaired following nerve injury and loss of NMJs is accelerated in a mouse model of amyotrophic lateral sclerosis (ALS). Here, we asked whether other microRNAs play similar roles. One attractive candidate is miR-133b because it is in the same transcript that encodes miR-206. Like miR-206, miR-133b is concentrated near NMJs and induced after denervation. In miR-133b null mice, however, NMJ development is unaltered, reinnervation proceeds normally following nerve injury, and disease progression is unaffected in the SOD1(G93A) mouse model of ALS. To determine if miR-206 compensates for the loss of miR-133b, we generated mice lacking both microRNAs. The phenotype of these double mutants resembled that of miR-206 single mutants. Finally, we used conditional mutants of Dicer, an enzyme required for the maturation of most microRNAs, to generate mice in which microRNAs were depleted from skeletal muscle fibers postnatally, thus circumventing a requirement for microRNAs in embryonic muscle development. Reinnervation of muscle fibers following injury was impaired in these mice, but the defect was similar in magnitude to that observed in miR-206 mutants. Together, these results suggest that miR-206 is the major microRNA that regulates repair of the NMJ following nerve injury. |
| first_indexed | 2024-09-23T15:04:30Z |
| format | Article |
| id | mit-1721.1/86187 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:04:30Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/861872022-10-02T00:24:54Z The Role of Muscle microRNAs in Repairing the Neuromuscular Junction Valdez, Gregorio Heyer, Mary P. Feng, Guoping Sanes, Joshua R. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Feng, Guoping microRNAs have been implicated in mediating key aspects of skeletal muscle development and responses to diseases and injury. Recently, we demonstrated that a synaptically enriched microRNA, miR-206, functions to promote maintenance and repair of the neuromuscular junction (NMJ); in mutant mice lacking miR-206, reinnervation is impaired following nerve injury and loss of NMJs is accelerated in a mouse model of amyotrophic lateral sclerosis (ALS). Here, we asked whether other microRNAs play similar roles. One attractive candidate is miR-133b because it is in the same transcript that encodes miR-206. Like miR-206, miR-133b is concentrated near NMJs and induced after denervation. In miR-133b null mice, however, NMJ development is unaltered, reinnervation proceeds normally following nerve injury, and disease progression is unaffected in the SOD1(G93A) mouse model of ALS. To determine if miR-206 compensates for the loss of miR-133b, we generated mice lacking both microRNAs. The phenotype of these double mutants resembled that of miR-206 single mutants. Finally, we used conditional mutants of Dicer, an enzyme required for the maturation of most microRNAs, to generate mice in which microRNAs were depleted from skeletal muscle fibers postnatally, thus circumventing a requirement for microRNAs in embryonic muscle development. Reinnervation of muscle fibers following injury was impaired in these mice, but the defect was similar in magnitude to that observed in miR-206 mutants. Together, these results suggest that miR-206 is the major microRNA that regulates repair of the NMJ following nerve injury. National Institutes of Health (U.S.) (NIH grant R01AG032322) National Institute of Neurological Disorders and Stroke (U.S.) (NRSA Postdoctoral Fellowship from NINDS/NIH) Ruth K. Broad Biomedical Research Foundation (Fellowship) McGovern Institute for Brain Research at MIT (Poitras Center for Affective Disorders Research) 2014-04-16T20:12:35Z 2014-04-16T20:12:35Z 2014-03 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/86187 Valdez, Gregorio, Mary P. Heyer, Guoping Feng, and Joshua R. Sanes. “The Role of Muscle microRNAs in Repairing the Neuromuscular Junction.” Edited by Lin Mei. PLoS ONE 9, no. 3 (March 24, 2014): e93140. https://orcid.org/0000-0002-8021-277X en_US http://dx.doi.org/10.1371/journal.pone.0093140 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science PLoS |
| spellingShingle | Valdez, Gregorio Heyer, Mary P. Feng, Guoping Sanes, Joshua R. The Role of Muscle microRNAs in Repairing the Neuromuscular Junction |
| title | The Role of Muscle microRNAs in Repairing the Neuromuscular Junction |
| title_full | The Role of Muscle microRNAs in Repairing the Neuromuscular Junction |
| title_fullStr | The Role of Muscle microRNAs in Repairing the Neuromuscular Junction |
| title_full_unstemmed | The Role of Muscle microRNAs in Repairing the Neuromuscular Junction |
| title_short | The Role of Muscle microRNAs in Repairing the Neuromuscular Junction |
| title_sort | role of muscle micrornas in repairing the neuromuscular junction |
| url | http://hdl.handle.net/1721.1/86187 https://orcid.org/0000-0002-8021-277X |
| work_keys_str_mv | AT valdezgregorio theroleofmusclemicrornasinrepairingtheneuromuscularjunction AT heyermaryp theroleofmusclemicrornasinrepairingtheneuromuscularjunction AT fengguoping theroleofmusclemicrornasinrepairingtheneuromuscularjunction AT sanesjoshuar theroleofmusclemicrornasinrepairingtheneuromuscularjunction AT valdezgregorio roleofmusclemicrornasinrepairingtheneuromuscularjunction AT heyermaryp roleofmusclemicrornasinrepairingtheneuromuscularjunction AT fengguoping roleofmusclemicrornasinrepairingtheneuromuscularjunction AT sanesjoshuar roleofmusclemicrornasinrepairingtheneuromuscularjunction |