| First Author | Kim Y | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 28139974 | Mgi Jnum | J:240931 |
| Mgi Id | MGI:5896850 | Doi | 10.7554/eLife.21303 |
| Citation | Kim Y, et al. (2017) The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 alpha-enhancer activity. Elife 6:e21303 |
| abstractText | 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 alpha-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 alpha-enhancer in the post-natal mouse retina. Tgfb1i1-/- mice show elevated alpha-enhancer activity leading to overproduction of Pax6DeltaPD 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 Pax6DeltaPBS/DeltaPBS mutation. Together, we show the antagonistic regulation of the alpha-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation. |
