The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity
- Korea Advanced Institute of Science and Technology, Republic of Korea
- Chungbuk National University School of Medicine, Republic of Korea
- The Catholic University of Korea, Republic of Korea
- Showa University School of Medicine, Japan
- Gwangju Institute of Science and Technology, Republic of Korea
- Vanderbilt University, United States
- 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
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
- 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
- Received: September 6, 2016
- Accepted: January 23, 2017
- Accepted Manuscript published: January 31, 2017 (version 1)
- 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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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
