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A comparative analysis of Otd/OTX function in the Drosophila eye: examining mechanisms of evolutionarily conserved function

Terrell, David A
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1385114250

Abstract Details

2013, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
Otd-related transcription factors are evolutionarily conserved to control anterior patterning and neurogenesis. Mutations in two human Otd-related gene products, OTX2 and CRX, associate with several photoreceptor-specific retinopathies and both factors are expressed in all photoreceptors from early specification through adulthood. However, it is not well understood how these factors function independently vs. redundantly, or how specific mutations in these factors lead to different disease outcomes. Drosophila encode a single Otd factor that has multiple functions during photoreceptor differentiation. In this work, we first define the functional domains of the Otd protein via a structure-function analysis. We then test the ability of human OTX1, OTX2, and CRX, as well as several disease-associated CRX alleles, to rescue the different functions of Otd. Our results indicate that: a) OTX2 and CRX rescue overlapping, yet distinct sub-functions of Otd during photoreceptor differentiation; b) CRX alleles can be functionally distinguished based on their rescue properties; and c) all three human Otd-related factors can rescue rhabdomeric photoreceptor morphogenesis. Together, the conserved functions of the Otd/OTX proteins suggest that the vertebrate OTX factors can interact with at least some of the same regulatory complexes as Otd in the Drosophila eye. Towards this end, I began to characterize the function of multiple Otd interaction partners in the Drosophila eye. We find that Otd genetically and physically interacts with a histone methyltransfesrase, G9a, and that this interaction is required to properly regulate the expression of specific Otd target genes (e.g. Rh5 expression). Overall, this work establishes the Drosophila eye as a unique model system to further study conserved functions of the OTX factors during photoreceptor development and differentiation.
Tiffany Cook, Ph.D. (Committee Chair)
Lionel Chow, M.D., Ph.D. (Committee Member)
Jun Ma, Ph.D. (Committee Member)
Elke Buschbeck, Ph.D. (Committee Member)
Kenneth Campbell, Ph.D. (Committee Member)
191 p.
Developmental Biology
rhodopsin; orthodenticle; eye; sense organ; congenital disease; retina

Recommended Citations

Citations

  • Terrell, D. A. (2013). A comparative analysis of Otd/OTX function in the Drosophila eye: examining mechanisms of evolutionarily conserved function [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1385114250

    APA Style (7th edition)

  • Terrell, David. A comparative analysis of Otd/OTX function in the Drosophila eye: examining mechanisms of evolutionarily conserved function. 2013. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1385114250.

    MLA Style (8th edition)

  • Terrell, David. "A comparative analysis of Otd/OTX function in the Drosophila eye: examining mechanisms of evolutionarily conserved function." Doctoral dissertation, University of Cincinnati, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1385114250

    Chicago Manual of Style (17th edition)

ucin1385114250
289
© 2013, some rights reserved.Creative Commons License A comparative analysis of Otd/OTX function in the Drosophila eye: examining mechanisms of evolutionarily conserved function by David A Terrell is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.