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 ofPaired-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, theTgfb1i1-/-mouse retinas show a sustained light response, which becomes more transient in mice with the auto-stimulation-defectivePax6ΔPBS/ΔPBSmutation. 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.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
authors.forename: Yeha
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
authors.forename: Taejeong
authors.initials: T
authors.lastname: Ha
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
authors.forename: You-Hyang
authors.initials: YH
authors.lastname: Song
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
authors.forename: Young-In
authors.initials: YI
authors.lastname: Sohn
authors.affiliation: Department of Physiology, Chungbuk National University School of Medicine, Cheongju, South Korea.
authors.forename: Dae-Jin
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Sun-Sook
authors.initials: SS
authors.lastname: Paik
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Joo-Ri
authors.initials: JR
authors.lastname: Kim-Kaneyama
authors.affiliation: Department of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea.
authors.forename: Mi-Ryoung
authors.initials: MR
authors.lastname: Song
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Leung
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, United States.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Levine
authors.affiliation: Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: In-Beom
authors.initials: IB
authors.lastname: Kim
authors.affiliation: Department of Physiology, Chungbuk National University School of Medicine, Cheongju, South Korea.
authors.forename: Yong Sook
authors.initials: YS
authors.lastname: Goo
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
authors.forename: Seung-Hee
authors.identifier: 0000-0002-9486-5771
authors.initials: SH
authors.lastname: Lee
authors.affiliation: KAIST Institute of BioCentury, Daejeon, South Korea.
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
authors.forename: Jin Woo
authors.identifier: 0000-0003-0767-1918
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000221:Adaptation, Ocular; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D060588:LIM Domain Proteins / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000071841:PAX6 Transcription Factor / Q000378:metabolism*; D012160:Retina / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; D000071841:PAX6 Transcription Factor; C000605732:Pax6 protein, mouse; C090090:Tgfb1i1 protein, mouse; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1
keywords: LIM domain protein; Pax6; cell fate determination; chromosomes; genes; mouse; neuroscience; retina; visual adaptation