The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity

  1. Yeha Kim
  2. Soyeon Lim
  3. Taejeong Ha
  4. You-Hyang Song
  5. Young-In Sohn
  6. Dae-Jin Park
  7. Sun-Soon Paik
  8. Joo-ri Kim-Kaneyama
  9. Mi-Ryoung Song
  10. Amanda Leung
  11. Edward M Levine
  12. In-Beom Kim
  13. Yong Sook Goo
  14. Seung-Hee Lee
  15. Kyung Hwa Kang
  16. Jin Woo Kim  Is a corresponding author
  1. Korea Advanced Institute of Science and Technology, Republic of Korea
  2. Chungbuk National University School of Medicine, Republic of Korea
  3. The Catholic University of Korea, Republic of Korea
  4. Showa University School of Medicine, Japan
  5. Gwangju Institute of Science and Technology, Republic of Korea
  6. Vanderbilt University, United States
  7. KAIST Institute of BioCentury, Republic of Korea

Abstract

The visual responses of vertebrates are sensitive to the overall composition of retinal interneurons including amacrine cells, which tune the activity of the retinal circuitry. The expression of Paired-homeobox 6 (PAX6) is regulated by multiple cis-DNA elements including the intronic α-enhancer, which is active in GABAergic amacrine cell subsets. Here, we report that Hydrogen peroxide-induced clone 5 (Hic5) interacts with the LIM domain transcription factors Lhx3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina. Hic5-/- mice show elevated α-enhancer activity leading to overproduction of Pax6ΔPD isoform that supports the GABAergic amacrine cell fate maintenance. Consequently, the Hic5-/- mouse retinas show a sustained light response, which becomes more transient in mice with the auto-stimulation-defective Pax6ΔPBS/ΔPBS mutation. Together, we show the antagonistic regulation of the α-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation.

Article and author information

Author details

  1. Yeha Kim

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  2. Soyeon Lim

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  3. Taejeong Ha

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  4. You-Hyang Song

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  5. Young-In Sohn

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  6. Dae-Jin Park

    Department of Physiology, Chungbuk National University School of Medicine, Cheongju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  7. Sun-Soon Paik

    Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  8. Joo-ri Kim-Kaneyama

    Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Mi-Ryoung Song

    Department of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  10. Amanda Leung

    Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Edward M Levine

    Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. In-Beom Kim

    Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  13. Yong Sook Goo

    Department of Physiology, Chungbuk National University School of Medicine, Cheongju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  14. Seung-Hee Lee

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9486-5771
  15. Kyung Hwa Kang

    KAIST Institute of BioCentury, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  16. Jin Woo Kim

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    For correspondence
    jinwookim@kaist.ac.kr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0767-1918

Funding

National Research Foundation of Korea (NRF-2009-00424)

  • Jin Woo Kim

National Research Foundation (NRF-2006-2004289)

  • Kyung Hwa Kang

National Eye Institute (NIH R01-EY013760)

  • Edward M Levine

National Research Foundation of Korea (NRF-2013-056566)

  • Jin Woo Kim

National Research Foundation of Korea (NRF-2014R1A2A2A01003069)

  • Jin Woo Kim

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

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Ethics

Animal experimentation: All experiments using mice were performed according to the regulations of the KAIST-IACUC (KA2012-38).

Version history

  1. Received: September 6, 2016
  2. Accepted: January 23, 2017
  3. Accepted Manuscript published: January 31, 2017 (version 1)
  4. Version of Record published: February 14, 2017 (version 2)

Copyright

© 2017, Kim 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. Yeha Kim
  2. Soyeon Lim
  3. Taejeong Ha
  4. You-Hyang Song
  5. Young-In Sohn
  6. Dae-Jin Park
  7. Sun-Soon Paik
  8. Joo-ri Kim-Kaneyama
  9. Mi-Ryoung Song
  10. Amanda Leung
  11. Edward M Levine
  12. In-Beom Kim
  13. Yong Sook Goo
  14. Seung-Hee Lee
  15. Kyung Hwa Kang
  16. Jin Woo Kim
(2017)
The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity
eLife 6:e21303.
https://doi.org/10.7554/eLife.21303

Share this article

https://doi.org/10.7554/eLife.21303

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