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David A. Terrell, Baotong Xie, Elizabeth McDonald, Michael Workman, Alison Nortman, Brian P. Brooks, Tiffany Cook; Modeling Retinal Disease in the Drosophila Eye. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1367.
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The otd/Otx family of transcription factors play evolutionarily conserved roles in anterior patterning, neural patterning and sensory organ formation from Drosophila to humans. Mutations in two Otx family members, CRX and OTX2, are associated with pediatric retinopathies such as Leber’s congenital amaurosis, retinitis pigmentosa, and cone-rod dystrophy. However, it currently remains unclear how specific mutations in these factors lead to specific disease outcomes. Drosophila otd, like human CRX and OTX2, plays pleiotropic roles in photoreceptor development. Thus, in this study we explore the possibility of using the Drosophila eye as a genetic system to identify conserved functions for CRX and OTX2 in photoreceptor development.
To address our primary objective to understand the conserved function of OTX1, OTX2, and CRX in the Drosophila eye, we took advantage of previously established in vitro and in vivo assays. First, we use a luciferase reporter assay to assess the ability of the vertebrate factors to activate the expression of multiple Drosophila opsin genes. Second, we examine the ability of the vertebrate factors to rescue proper development of the eye in the absence of Drosophila otd.
Our data indicates that the vertebrate otd-related factors have overlapping yet distinct abilities to function in the Drosophila eye. While CRX has the greatest conserved ability to rescue Drosophila eye development in the absence of otd, OTX1 and OTX2 also rescue specific aspects of eye development. Moreover, we show that CRX mutations known to cause Leber’s congenital amaurosis differentially rescue Drosophila eye morphology and proper opsin expression.
This study demonstrates that each of the vertebrate otd-related factors contain conserved functions of otd and provides a basis for utilizing the Drosophila eye as a tool to further study the function of these factors. Moreover, the Drosophila eye will serve as a relatively quick, in vivo model to systematically examine numerous disease-causing mutations of CRX.
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