The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 ?-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 ?-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 ?-enhancer in the post-natal mouse retina. Tgfb1i1-/- mice show elevated ?-enhancer activity leading to overproduction of Pax6?PD 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?PBS/?PBS mutation. Together, we show the antagonistic regulation of the ?-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation.

SUBMITTER: Kim Y 

PROVIDER: S-EPMC5308899 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature