title: OTX2 and CRX rescue overlapping and photoreceptor-specific functions in the Drosophila eye.
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.
authors: Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors: David
authors: D
authors: Terrell
authors: Baotong
authors: B
authors: Xie
authors: Michael
authors: M
authors: Workman
authors: Simpla
authors: S
authors: Mahato
authors: Andrew
authors: A
authors: Zelhof
authors: Brian
authors: B
authors: Gebelein
authors: Tiffany
authors: T
authors: Cook
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology* / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009024:Morphogenesis / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; D015534:Trans-Activators; C109288:cone rod homeobox protein