Transcriptional control of motor pool formation and motor circuit connectivity by the LIM-HD protein Isl2
- Gwangju Institute of Science and Technology, Republic of Korea
- World Institute of Kimchi, Republic of Korea
- Korea Institute of Toxicology, Republic of Korea
- Dong-A University, Republic of Korea
- Samsung Medical Center, Republic of Korea
- Korea Brain Research Institute, Republic of Korea
- 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
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Transcriptional control of motor pool formation and motor circuit connectivity by the LIM-HD protein Isl2NCBI Gene Expression Omnibus, GSE217297.
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Author details
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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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
