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Author Notes:

Correspondence: Xinyu Zhao, Ph.D., Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131; Email: xzhao@salud.unm.edu and Peng Jin, Ph.D., Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 3032; Email: peng.jin@emory.edu

Authors' Contributions: Richard Smrt: Concept and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript

Keith Szulwach: Collection and/or assembly of data, data analysis and interpretation, final approval of manuscript

Rebecca Pfeiffer: Collection of data

See publication for full list of author contributions.

Acknowledgments: We would like to thank the members of the Zhao and Jin Laboratories for their helpful discussions.

We thank F. H. Gage for providing us the lentiviral vector and retroviral vector used to engineer the expression vectors for miR-137.

Thanks to Michael C. Wilson and Lawrence Tafoya for providing training in neuronal culture methods.

Disclosures: The authors declare that they have no conflict of interest.

Subjects:

Research Funding:

This work was supported by grants from NIH (MH080434, MH07897) and International Rett Syndrome Foundation (IRSF) to XZ; a Minority Supplement (MH080434) to RDS; Institutional Minority Student Development program (IMSD, NIH 2R25GM060201-09) to RLP; grants from NIH (NS051630 and MH076090) and IRSF to PJ.

P.J. is the recipient of a Beckman Young Investigator Award, Basil O’Connor Scholar Research Award, and Alfred P. Sloan Research Fellow in Neuroscience.

X.L. was a recipient of the Autism Speaks Postdoctoral Fellowship.

Keywords:

  • miR-137
  • microRNA
  • neural stem cells
  • adult neurogenesis
  • dendritic development
  • neuronal maturation

MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase Mind Bomb-1

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Journal Title:

STEM CELLS

Volume:

Volume 28, Number 6

Publisher:

, Pages 1060-1070

Type of Work:

Article | Post-print: After Peer Review

Abstract:

A final step of neurogenesis is the maturation of young neurons, which is regulated by complex mechanisms and dysregulation of this process is frequently found in neurodevelopmental disorders. MicroRNAs have been implicated in several steps of neuronal maturation including dendritic and axonal growth, spine development, and synaptogenesis. We demonstrate that one brain-enriched microRNA, miR-137, has a significant role in regulating neuronal maturation. Overexpression of miR-137 inhibits dendritic morphogenesis, phenotypic maturation, and spine development both in brain and cultured primary neurons. On the other hand, a reduction in miR-137 had opposite effects. We further show that miR-137 targets the Drosophila Mib1 protein through the conserved target site located in the 3′ untranslated region of Mib1 mRNA. Mib1 is an ubiquitin ligase known to be important for neurodevelopment. We show that exogenously expressed Mib1 could partially rescue the phenotypes associated with miR-137 overexpression. These results demonstrate a novel miRNA-mediated mechanism involving miR-137 and Mib1 that function to regulate neuronal maturation and dendritic morphogenesis during development.

Copyright information:

© 2010 AlphaMed Press

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