MicroRNAs mediate precise control of spinal interneuron populations to exert delicate sensory-to-motor outputs

Abstract

Although the function of microRNAs (miRNAs) during embryonic development has been intensively studied in recent years, their postnatal physiological functions remain largely unexplored due to inherent difficulties with the presence of redundant paralogs of the same seed. Thus, it is particularly challenging to uncover miRNA functions at neural circuit level since animal behaviors would need to be assessed upon complete loss of miRNA family functions. Here, we focused on the neural functions of MiR34/449 that manifests a dynamic expression pattern in the spinal cord from embryonic to postnatal stages. Our behavioral assays reveal that the loss of MiR34/449 miRNAs perturb thermally-induced pain response thresholds and compromised delicate motor output in mice. Mechanistically, MiR34/449 directly target Satb1 and Satb2 to fine-tune the precise number of a sub-population of motor synergy encoder (MSE) neurons. Thus, MiR34/449 fine-tunes optimal development of Satb1/2on interneurons in the spinal cord, thereby refining explicit sensory-to-motor circuit outputs.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for supplementary video1 and 2.The R analysis script written for this paper is available at https://gitlab.com/jaclab/mir-34_449.

Article and author information

Author details

  1. Shih-Hsin Chang

    Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2821-7095
  2. Yi-Ching Su

    Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2760-9540
  3. Mien Chang

    Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  4. Jun-An Chen

    Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
    For correspondence
    jachen@imb.sinica.edu.tw
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9870-3203

Funding

Ministry of Science and Technology, Taiwan (109-2811-B-001-546-)

  • Jun-An Chen

Ministry of Science and Technology, Taiwan (108-2311-B-001-011-)

  • Jun-An Chen

Ministry of Science and Technology, Taiwan (107-2311-B-001-043-)

  • Jun-An Chen

National Health Research Institutes (NHRI-EX108-10831NI)

  • Jun-An Chen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Version history

  1. Received: October 6, 2020
  2. Accepted: March 19, 2021
  3. Accepted Manuscript published: March 31, 2021 (version 1)
  4. Version of Record published: April 26, 2021 (version 2)

Copyright

© 2021, Chang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Shih-Hsin Chang
  2. Yi-Ching Su
  3. Mien Chang
  4. Jun-An Chen
(2021)
MicroRNAs mediate precise control of spinal interneuron populations to exert delicate sensory-to-motor outputs
eLife 10:e63768.
https://doi.org/10.7554/eLife.63768

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https://doi.org/10.7554/eLife.63768

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