Mef2d is essential for the maturation and integrity of retinal photoreceptor and bipolar cells

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2015-05, Vol.20 (5), p.408-426
• Main Authors: Omori, Yoshihiro, Kitamura, Tamiki, Yoshida, Satoyo, Kuwahara, Ryusuke, Chaya, Taro, Irie, Shoichi, Furukawa, Takahisa
• Format: Article
• Language: English
• Subjects: Animals; Arrestins - genetics; Cell Differentiation - genetics; Electroretinography; Gene expression; Gene Expression Regulation, Developmental; Homeodomain Proteins - metabolism; MEF2 Transcription Factors - genetics; MEF2 Transcription Factors - metabolism; Mice; Mice, Knockout; Photoreceptor Cells, Vertebrate - cytology; Photoreceptor Cells, Vertebrate - metabolism; Photoreceptor Cells, Vertebrate - pathology; Photoreceptor Cells, Vertebrate - ultrastructure; Photoreceptors; Promoter Regions, Genetic; Protein Binding; Retinal Bipolar Cells - cytology; Retinal Bipolar Cells - metabolism; Retinal Bipolar Cells - pathology; Retinal Bipolar Cells - ultrastructure; Retinal Degeneration - genetics; Retinal Degeneration - pathology; Retinal Photoreceptor Cell Inner Segment - metabolism; Retinal Photoreceptor Cell Inner Segment - pathology; Retinal Photoreceptor Cell Outer Segment - metabolism; Rodents; Synapses - genetics; Synapses - metabolism; Trans-Activators - metabolism; Transcription, Genetic
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12233

Mef2 transcription factors play a crucial role in cardiac and skeletal muscle differentiation. We found that Mef2d is highly expressed in the mouse retina and its loss causes photoreceptor degeneration similar to that observed in human retinitis pigmentosa patients. Electroretinograms (ERGs) were severely impaired in Mef2d−/− mice. Immunohistochemistry showed that photoreceptor and bipolar cell synapse protein levels severely decreased in the Mef2d−/− retina. Expression profiling by microarray analysis showed that Mef2d is required for the expression of various genes in photoreceptor and bipolar cells, including cone arrestin, Guca1b, Pde6h and Cacna1s, which encode outer segment and synapse proteins. We also observed that Mef2d synergistically activates the cone arrestin (Arr3) promoter with Crx, suggesting that functional cooperation between Mef2d and Crx is important for photoreceptor cell gene regulation. Taken together, our results show that Mef2d is essential for photoreceptor and bipolar cell gene expression, either independently or cooperatively with Crx.