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

David Terrell, Baotong Xie, Michael Workman, Simpla Mahato, Andrew Zelhof, Brian Gebelein, Tiffany Cook

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)215-228
Number of pages14
JournalDevelopmental Dynamics
Volume241
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • Congenital disease
  • Eye
  • Orthodenticle
  • Retina
  • Rhodopsin
  • Sense organ

ASJC Scopus subject areas

  • Developmental Biology

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