The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity.
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 Pax6 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.
['Kim|Yeha|Y|', 'Lim|Soyeon|S|', 'Ha|Taejeong|T|', 'Song|You-Hyang|YH|', 'Sohn|Young-In|YI|', 'Park|Dae-Jin|DJ|', 'Paik|Sun-Sook|SS|', 'Kim-Kaneyama|Joo-Ri|JR|', 'Song|Mi-Ryoung|MR|', 'Leung|Amanda|A|', 'Levine|Edward M|EM|', 'Kim|In-Beom|IB|', 'Goo|Yong Sook|YS|', 'Lee|Seung-Hee|SH|0000-0002-9486-5771', 'Kang|Kyung Hwa|KH|', 'Kim|Jin Woo|JW|0000-0003-0767-1918']
D000221:Adaptation, Ocular D000818:Animals D003598:Cytoskeletal Proteins D004268:DNA-Binding Proteins D004742:Enhancer Elements, Genetic D005786:Gene Expression Regulation D060588:LIM Domain Proteins D060850:LIM-Homeodomain Proteins D051379:Mice D018345:Mice, Knockout D000071841:PAX6 Transcription Factor D012160:Retina D014157:Transcription Factors
visual adaptation Pax6 mouse retina LIM domain protein cell fate determination chromosomes genes neuroscience