OTX2 and CRX rescue overlapping and photoreceptor-specific functions in the Drosophila eye

Authors

  • David Terrell,

    1. Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    2. Molecular and Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, Ohio
    3. Physician Scientists Training Program, University of Cincinnati, Cincinnati, Ohio
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  • Baotong Xie,

    1. Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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  • Michael Workman,

    1. Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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  • Simpla Mahato,

    1. Department of Biology, Indiana University, Bloomington, Indiana
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  • Andrew Zelhof,

    1. Department of Biology, Indiana University, Bloomington, Indiana
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  • Brian Gebelein,

    1. Molecular and Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, Ohio
    2. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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  • Tiffany Cook

    Corresponding author
    1. Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    2. Molecular and Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, Ohio
    3. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    • Divisions of Pediatric Ophthalmology and Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 7003, Cincinnati, OH 45229

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Abstract

Background: Otd-related transcription factors are evolutionarily conserved to control anterior patterning and neurogenesis. In humans, two such factors, OTX2 and CRX, are expressed in all photoreceptors from early specification through adulthood and associate with several photoreceptor-specific retinopathies. It is not well understood how these factors function independently vs. redundantly, or how specific mutations lead to different disease outcomes. It is also unclear how OTX1 and OTX2 functionally overlap during other aspects of neurogenesis and ocular development. Drosophila encodes a single Otd factor that has multiple functions during eye development. Using the Drosophila eye as a model, we tested the ability of the human OTX1, OTX2, and CRX genes, as well as several disease-associated CRX alleles, to rescue the different functions of Otd. Results: Our results indicate the following: OTX2 and CRX display overlapping, yet distinct subfunctions of Otd during photoreceptor differentiation; CRX disease alleles can be functionally distinguished based on their rescue properties; and all three factors are able to rescue rhabdomeric photoreceptor morphogenesis. Conclusions: Our findings have important implications for understanding how Otx proteins have subfunctionalized during evolution, and cement Drosophila as an effective tool to unravel the molecular bases of photoreceptor pathogenesis. Developmental Dynamics 241:215–228, 2012. © 2011 Wiley Periodicals, Inc.

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