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

Yeha Kim; Soyeon Lim; Taejeong Ha; You Hyang Song; Young In Sohn; Dae Jin Park; Sun Sook Paik; Joo Ri Kim-Kaneyama; Mi Ryoung Song; Amanda Leung; Edward M. Levine; In Beom Kim; Yong Sook Goo; Seung Hee Lee; Kyung Hwa Kang; Jin Woo Kim

doi:10.7554/eLife.21303

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

Yeha Kim, Soyeon Lim, Taejeong Ha, You Hyang Song, Young In Sohn, Dae Jin Park, Sun Sook Paik, Joo Ri Kim-Kaneyama, Mi Ryoung Song, Amanda Leung, Edward M. Levine, In Beom Kim, Yong Sook Goo, Seung Hee Lee, Kyung Hwa Kang, Jin Woo Kim

Department of Anatomy

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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 the transforming growth factor ß1-induced transcript 1 protein (Tgfb1i1) interacts with the LIM domain transcription factors Lh×3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina. Tgfb1i1^-/- mice show elevated a-enhancer activity leading to overproduction of Pax6ΔPD isoform that supports the GABAergic amacrine cell fate maintenance. Consequently, the Tgfb1i1^-/- mouse retinas show a sustained light response, which becomes more transient in mice with the auto-stimulation-defective Pax6^ΔPBS/ΔPBS mutation. Together, we show the antagonistic regulation of the a-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation.

Original language	English
Article number	e21303
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.21303
State	Published - 31 Jan 2017

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© Kim et al.

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10.7554/eLife.21303

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Kim, Y., Lim, S., Ha, T., Song, Y. H., Sohn, Y. I., Park, D. J., Paik, S. S., Kim-Kaneyama, J. R., Song, M. R., Leung, A., Levine, E. M., Kim, I. B., Goo, Y. S., Lee, S. H., Kang, K. H., & Kim, J. W. (2017). The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity. eLife, 6, Article e21303. https://doi.org/10.7554/eLife.21303

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

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 the transforming growth factor {\ss}1-induced transcript 1 protein (Tgfb1i1) interacts with the LIM domain transcription factors Lh×3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina. Tgfb1i1-/- mice show elevated a-enhancer activity leading to overproduction of Pax6ΔPD isoform that supports the GABAergic amacrine cell fate maintenance. Consequently, the Tgfb1i1-/- 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 a-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation.",

author = "Yeha Kim and Soyeon Lim and Taejeong Ha and Song, {You Hyang} and Sohn, {Young In} and Park, {Dae Jin} and Paik, {Sun Sook} and Kim-Kaneyama, {Joo Ri} and Song, {Mi Ryoung} and Amanda Leung and Levine, {Edward M.} and Kim, {In Beom} and Goo, {Yong Sook} and Lee, {Seung Hee} and Kang, {Kyung Hwa} and Kim, {Jin Woo}",

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AU - Kim, Yeha

AU - Lim, Soyeon

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AU - Song, You Hyang

AU - Sohn, Young In

AU - Park, Dae Jin

AU - Paik, Sun Sook

AU - Kim-Kaneyama, Joo Ri

AU - Song, Mi Ryoung

AU - Leung, Amanda

AU - Levine, Edward M.

AU - Kim, In Beom

AU - Goo, Yong Sook

AU - Lee, Seung Hee

AU - Kang, Kyung Hwa

AU - Kim, Jin Woo

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N2 - 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 the transforming growth factor ß1-induced transcript 1 protein (Tgfb1i1) interacts with the LIM domain transcription factors Lh×3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina. Tgfb1i1-/- mice show elevated a-enhancer activity leading to overproduction of Pax6ΔPD isoform that supports the GABAergic amacrine cell fate maintenance. Consequently, the Tgfb1i1-/- 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 a-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation.

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

Abstract

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