| Popis: |
From flies to humans, Orthodenticle (Otd)-related homeodomain transcription factors are necessary for eye development. Vertebrates encode three Otd-related factors, Otx1, Otx2 and Crx, while Drosophila encodes a single factor, Otd. Mutations in Otx2 or Crx can lead to eye diseases by affecting morphogenesis or maintenance of photoreceptors. In the Drosophila eye, Otd has been found to play a conserved role and is likewise necessary for photoreceptor morphogenesis and subtype specification during terminal differentiation. This latter function occurs through cell-specific activation and repression of known target genes. However, the mechanism of how Otd regulates transcription remains unknown. To address this question, we performed an in vitro analysis of Otd to identify functional domains and found that Otd contains two independent activation domains, one at the N and C-terminus, and a potential repression domain centrally located in the protein. These results suggest that multiple domains of Otd contribute to regulating gene expression of different targets through different mechanisms. We also tested whether Otd plays a post-developmental role in photoreceptor maintenance, like Crx and Otx2 in vertebrates. Our preliminary results suggested that Otd may be important in the adult eye. We next investigated if the domains identified from the in vitro study were necessary in vivo for photoreceptor maintenance. Our results show that morphogenesis and maintenance of photoreceptors require different domains, and that the C-terminus is likely important for photoreceptor integrity. This system can further be used to study photoreceptor degeneration to better understand the mechanisms of eye disease. |
