Critical roles of ARHGAP36 as a signal transduction mediator of Shh pathway in lateral motor columnar specification

  1. Heejin Nam
  2. Shin Jeon
  3. Hyejin An
  4. Jaeyoung Yoo
  5. Hyo-Jong Lee
  6. Soo-Kyung Lee
  7. Seunghee Lee  Is a corresponding author
  1. Seoul National University, Korea (South), Republic of
  2. Inje University, Korea (South), Republic of
  3. Oregon Health and Science University, United States

Abstract

During spinal cord development, Sonic hedgehog (Shh), secreted from the floor plate, plays an important role in the production of motor neurons by patterning the ventral neural tube, which establishes MN progenitor identity. It remains unknown, however, if Shh signaling plays a role in generating columnar diversity of MNs that connect distinct target muscles. Here, we report that Shh, expressed in MNs, is essential for the formation of lateral motor column (LMC) neurons in vertebrate spinal cord. This novel activity of Shh is mediated by its downstream effector ARHGAP36, whose expression is directly induced by the MN-specific transcription factor complex Isl1-Lhx3. Furthermore, we found that AKT stimulates the Shh activity to induce LMC MNs through the stabilization of ARHGAP36 proteins. Taken together, our data reveal that Shh, secreted from MNs, plays a crucial role in generating MN diversity via a regulatory axis of Shh-AKT-ARHGAP36 in the developing mouse spinal cord.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Heejin Nam

    College of Pharmacy, Seoul National University, Seoul, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.
  2. Shin Jeon

    College of Pharmacy, Seoul National University, Seoul, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.
  3. Hyejin An

    College of Pharmacy, Seoul National University, Seoul, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.
  4. Jaeyoung Yoo

    College of Pharmacy, Seoul National University, Seoul, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.
  5. Hyo-Jong Lee

    College of Pharmacy, Inje University, Gimhae, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4826-7954
  6. Soo-Kyung Lee

    Department of Pediatrics, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1745-256X
  7. Seunghee Lee

    College of Pharmacy, Seoul National University, Seoul, Korea (South), Republic of
    For correspondence
    leeseung@snu.ac.kr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5483-0016

Funding

Korea Health Industry Development Institute (HI17C0447)

  • Seunghee Lee

National Institute of Neurological Disorders and Stroke (R01NS100471)

  • Soo-Kyung Lee

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

Reviewing Editor

  1. Francois Guillemot, The Francis Crick Institute, United Kingdom

Ethics

Animal experimentation: All mouse works were performed under an approved protocol (SNU-150123-1-2) by the Institutional Animal Care and Use Committee (IACUC) at Seoul National University.

Version history

  1. Received: March 8, 2019
  2. Accepted: July 14, 2019
  3. Accepted Manuscript published: July 15, 2019 (version 1)
  4. Version of Record published: July 25, 2019 (version 2)

Copyright

© 2019, Nam 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. Heejin Nam
  2. Shin Jeon
  3. Hyejin An
  4. Jaeyoung Yoo
  5. Hyo-Jong Lee
  6. Soo-Kyung Lee
  7. Seunghee Lee
(2019)
Critical roles of ARHGAP36 as a signal transduction mediator of Shh pathway in lateral motor columnar specification
eLife 8:e46683.
https://doi.org/10.7554/eLife.46683

Share this article

https://doi.org/10.7554/eLife.46683

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