The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28139974.
- Also identified by DOI 10.7554/eLife.21303 and PMC identifier 5308899.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Paired-homeobox 6 (PAX6)</i> 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. <i>Tgfb1i1<sup>-/-</sup></i> mice show elevated α-enhancer activity leading to overproduction of Pax6ΔPD isoform that supports the GABAergic amacrine cell fate maintenance. Consequently, the <i>Tgfb1i1<sup>-/-</sup></i> mouse retinas show a sustained light response, which becomes more transient in mice with the auto-stimulation-defective <i>Pax6<sup>ΔPBS/ΔPBS</sup></i> 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.
Medical subject headings
- Cytoskeletal Proteins
- DNA-Binding Proteins
- Enhancer Elements, Genetic
- Gene Expression Regulation
- LIM Domain Proteins
- LIM-Homeodomain Proteins
- PAX6 Transcription Factor
- Retina
- Transcription Factors