Transcriptional control of motor pool formation and motor circuit connectivity by the LIM-HD protein Isl2

  1. Yunjeong Lee
  2. In Seo Yeo
  3. Namhee Kim
  4. Dong-Keun Lee
  5. Kyung-Tai Kim
  6. Jiyoung Yoon
  7. Jawoon Yi
  8. Young Bin Hong
  9. Byung-Ok Choi
  10. Yoichi Kosodo
  11. Daesoo Kim
  12. Jihwan Park
  13. Mi-Ryoung Song  Is a corresponding author
  1. Gwangju Institute of Science and Technology, Republic of Korea
  2. World Institute of Kimchi, Republic of Korea
  3. Korea Institute of Toxicology, Republic of Korea
  4. Dong-A University, Republic of Korea
  5. Samsung Medical Center, Republic of Korea
  6. Korea Brain Research Institute, Republic of Korea
  7. Korea Advanced Institute of Science and Technology, Republic of Korea

Abstract

The fidelity of motor control requires the precise positional arrangement of motor pools and the establishment of synaptic connections between them. During neural development in the spinal cord, motor nerves project to specific target muscles and receive proprioceptive input from these muscles via the sensorimotor circuit. LIM-homeodomain transcription factors are known to play a crucial role in successively restricting specific motor neuronal fates. However, their exact contribution to limb-based motor pools and locomotor circuits has not been fully understood. To address this, we conducted an investigation into the role of Isl2, a LIM-homeodomain transcription factor, in motor pool organization. We found that deletion of Isl2 led to the dispersion of motor pools, primarily affecting the median motor column and lateral LMC (LMCl) populations. Additionally, hindlimb motor pools lacked Etv4 expression, and we observed reduced terminal axon branching and disorganized neuromuscular junctions in Isl2-deficient mice. Furthermore, we performed transcriptomic analysis on the spinal cords of Isl2-deficient mice and identified a variety of downregulated genes associated with motor neuron (MN) differentiation, axon development, and synapse organization in hindlimb motor pools. As a consequence of these disruptions, sensorimotor connectivity and hindlimb locomotion were impaired in Isl2-deficient mice. Taken together, our findings highlight the critical role of Isl2 in organizing motor pool position and sensorimotor circuits in hindlimb motor pools. This research provides valuable insights into the molecular mechanisms governing motor control and its potential implications for understanding motor-related disorders in humans.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE217297

The following data sets were generated

Article and author information

Author details

  1. Yunjeong Lee

    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  2. In Seo Yeo

    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  3. Namhee Kim

    Fermentation Regulation Technology Research Group, World Institute of Kimchi, Gwangju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  4. Dong-Keun Lee

    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  5. Kyung-Tai Kim

    Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  6. Jiyoung Yoon

    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  7. Jawoon Yi

    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  8. Young Bin Hong

    Department of Biochemistry, Dong-A University, Busan, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  9. Byung-Ok Choi

    Department of Neurology, Samsung Medical Center, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  10. Yoichi Kosodo

    Korea Brain Research Institute, Daegu, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  11. Daesoo Kim

    Department of Brain and Cognitive Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  12. Jihwan Park

    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5728-912X
  13. Mi-Ryoung Song

    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
    For correspondence
    msong@gist.ac.kr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0350-0863

Funding

National Research Foundation of Korea (NRF-2018R1A5A1024261)

  • Mi-Ryoung Song

National Research Foundation of Korea (NRF-2022M3E5E8081194)

  • Mi-Ryoung Song

National Research Foundation of Korea (NRF-2023R1A2C1002690)

  • Mi-Ryoung Song

Gwangju Institute of Science and Technology (the GIST Research Institute in 2023)

  • Mi-Ryoung Song

the Kun-hee Lee Child Cancer & Rare Disease Research Foundation (22B-001-0500)

  • Mi-Ryoung Song

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Gwangju Institute of Science and Technology (GIST, No. GIST2021-072). All mice were housed and cared for in an Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC)-accredited animal facility under specific pathogen-free conditions.

Copyright

© 2023, Lee 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. Yunjeong Lee
  2. In Seo Yeo
  3. Namhee Kim
  4. Dong-Keun Lee
  5. Kyung-Tai Kim
  6. Jiyoung Yoon
  7. Jawoon Yi
  8. Young Bin Hong
  9. Byung-Ok Choi
  10. Yoichi Kosodo
  11. Daesoo Kim
  12. Jihwan Park
  13. Mi-Ryoung Song
(2023)
Transcriptional control of motor pool formation and motor circuit connectivity by the LIM-HD protein Isl2
eLife 12:e84596.
https://doi.org/10.7554/eLife.84596

Share this article

https://doi.org/10.7554/eLife.84596

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