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miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3

Author

Listed:
  • Karen P. Thiebes

    (Pediatric Neuroscience Research Program, Papé Family Pediatric Research Institute)

  • Heejin Nam

    (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)

  • Xiaolu A. Cambronne

    (Vollum Institute)

  • Rongkun Shen

    (Vollum Institute
    Present address: Department of Biology, College at Brockport, SUNY, Brockport, New York, New York 14420, USA)

  • Stacey M. Glasgow

    (Center for Cell and Gene Therapy, Baylor College of Medicine)

  • Hyong-Ho Cho

    (Pediatric Neuroscience Research Program, Papé Family Pediatric Research Institute
    Chonnam National University Medical School)

  • Ji-sun Kwon

    (Pediatric Neuroscience Research Program, Papé Family Pediatric Research Institute)

  • Richard H. Goodman

    (Vollum Institute)

  • Jae W. Lee

    (Pediatric Neuroscience Research Program, Papé Family Pediatric Research Institute
    Oregon Health & Science University)

  • Seunghee Lee

    (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)

  • Soo-Kyung Lee

    (Pediatric Neuroscience Research Program, Papé Family Pediatric Research Institute
    Vollum Institute
    Oregon Health & Science University)

Abstract

While microRNAs have emerged as an important component of gene regulatory networks, it remains unclear how microRNAs collaborate with transcription factors in the gene networks that determines neuronal cell fate. Here we show that in the developing spinal cord, the expression of miR-218 is directly upregulated by the Isl1–Lhx3 complex, which drives motor neuron fate. Inhibition of miR-218 suppresses the generation of motor neurons in both chick neural tube and mouse embryonic stem cells, suggesting that miR-218 plays a crucial role in motor neuron differentiation. Results from unbiased RISC-trap screens, in vivo reporter assays and overexpression studies indicated that miR-218 directly represses transcripts that promote developmental programs for interneurons. In addition, we found that miR-218 activity is required for Isl1–Lhx3 to effectively induce motor neurons and suppress interneuron fates. Together our results reveal an essential role of miR-218 as a downstream effector of the Isl1–Lhx3 complex in establishing motor neuron identity.

Suggested Citation

  • Karen P. Thiebes & Heejin Nam & Xiaolu A. Cambronne & Rongkun Shen & Stacey M. Glasgow & Hyong-Ho Cho & Ji-sun Kwon & Richard H. Goodman & Jae W. Lee & Seunghee Lee & Soo-Kyung Lee, 2015. "miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8718
    DOI: 10.1038/ncomms8718
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    Cited by:

    1. Wenxian Wang & Hyeyoung Cho & Jae W. Lee & Soo-Kyung Lee, 2022. "The histone demethylase Kdm6b regulates subtype diversification of mouse spinal motor neurons during development," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    2. Peter Langfelder & Fuying Gao & Nan Wang & David Howland & Seung Kwak & Thomas F Vogt & Jeffrey S Aaronson & Jim Rosinski & Giovanni Coppola & Steve Horvath & X William Yang, 2018. "MicroRNA signatures of endogenous Huntingtin CAG repeat expansion in mice," PLOS ONE, Public Library of Science, vol. 13(1), pages 1-20, January.

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