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

Autor: 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
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: eLife, Vol 6 (2017)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.21303
Popis: 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 Lhx3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina. Tgfb1i1-/- mice show elevated α-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 α-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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